According to Statistics Canada, gastrointestinal (GI) diseases are responsible for over 300,000 deaths each year in Canada across all ages (3). GI diseases are predicted to increase over the next ten years and can impact human health on a global level. Common causes of digestive issues within our population involve chronic stress, harmful pesticides, and the consumption of the Standard American Diet (3)(4).
After identifying this increase in disease prevalence, researchers are aware that there is a gap in diagnostic technology assessing GI symptoms. By turning to the world of smart medical devices, we open up a variety of options for GI disease diagnosis. One of these examples is the SmartPill device.
The SmartPill is a wireless capsule that a physician can use which monitors parameters such as pH, pressure, gastrointestinal transit time, and temperature throughout your digestive tract (5). The capsule is currently approved by the FDA for the diagnosis of conditions that are related to gastric emptying delays and general gastrointestinal motility disease (6).
SOURCE: BASS Medical Group (1)
The SmartPill functions as an endoscopic capsule. Patients swallow an activated wireless pH, pressure, and temperature capsule. This capsule contains sensors that measure pH (with a range of 0.5-9), temperature (with a range of 25-49 °C), and pressure (with a range of 0-350 mmHg) (5). After ingestion, the capsule signals are transmitted from within the GI tract and captured by a receiver. The data receiver is a portable device worn on a belt or a lanyard by the patient and it records information collected by the capsule (5). The data is then stored in the device and transmitted to a computer which provides the physician with the necessary information to evaluate the function of the patient’s stomach and intestines. The patient then continues with their day-to-day activities, and the pill is usually passed within 1-2 days. After passing the pill, the patient returns the data recorder to the physician’s office where the results are then analyzed.
SOURCE: Wang et. al (2)
The current standard of care for diagnostic procedures involves invasive or uncomfortable methods such as upper GI barium swallow tests, gastroscopy, endoscopy, or gastric manometry. The use of the SmartPill, however, may mitigate patient discomfort due to its ingestible approach. For the reliability of results, a study was done assessing the clinical use of wireless motility capsules. The SmartPill capsule detected a generalized motility disorder in 51% of patients (7). The capsule was also shown to influence management decisions in 30% of patients with lower GI disorders and 88% of patients with upper GI disorders (8). These results show that the SmartPill can function as an advantage to our healthcare system by comfortably assessing gastrointestinal parameters, allowing seamless data collection, and providing physicians with assistance for disease management.
Browning KN, Travagli RA. Central Nervous System Control of Gastrointestinal Motility and Secretion and Modulation of Gastrointestinal Functions. Compr Physiol. 2014 Oct;4(4):1339–68.
Tu P, Chi L, Bodnar W, Zhang Z, Gao B, Bian X, et al. Gut Microbiome Toxicity: Connecting the Environment and Gut Microbiome-Associated Diseases. Toxics. 2020 Mar 12;8(1):19.
Cassilly D, Kantor S, Knight LC, Maurer AH, Fisher RS, Semler J, et al. Gastric emptying of a non-digestible solid: assessment with simultaneous SmartPill pH and pressure capsule, antroduodenal manometry, gastric emptying scintigraphy. Neurogastroenterol Motil. 2008;20(4):311–9.
You may have come across the term designer babies in recent years as the topic has started to rise in popularity. Although they may sound like babies who cruise around town in their Gucci baby stroller, snuggled up in their Louis Vuitton onesie, the reality is much more fascinating. Unfortunately, however, many still need to be made aware of the actual science, methods, and implications of the development of designer babies and how we may already be seeing the application of this technology all around us.
The idea of designer babies was initially proposed to reduce or avoid heritable diseases coded by mutations in our DNA, creating healthy and happier babies (1). This process is done by editing the genome through methods such as preimplantation genetic diagnosis or genetic modification (1).
SOURCE: inviTRA
Preimplantation genetic diagnosis (PGD) is the process of genetic testing of an embryo before it is implanted in the uterus and is used in conjunction with in vitro fertilization (IVF) (2). PGD identifies potential genetic abnormalities in embryos before embryo transfer (implanting a newly formed embryo into the woman’s uterus), commonly used to prevent single-gene conditions such as cystic fibrosis or sickle cell anemia (3). For example, in sickle cell anemia, a single allele point mutation can be targeted. However, more complex conditions such as autism involve the interaction of many genes and the environment and cannot be targeted or even understood as thoroughly. Despite this, PGD is available for all inherited conditions where the exact mutation is known and can be tested on the embryo (3).
The possibilities with PGD are still in development, and although the technique still suffers from limitations, it is a practical and more sensible approach to reducing heritable diseases.
However, the idea of the designer baby in popular culture has taken a new meaning and often refers to the use of genomic editing technologies for purposes beyond simply reducing heritable disease (1). Unlike PGD, the topic of gene editing in humans is an ever-changing debate on the ethics, morality, and beliefs regarding this technology’s political and social implications. Nevertheless, individuals have already begun creating babies with edited genomes and engineered mutations (4).
Individuals may take advantage of this technology to create babies with certain facial features and physical characteristics such as coloured eyes, athletic builds, and taller bodies. However, using genomic editing to create babies with “ideal” features strongly reinforces stereotypes and prejudice against people with features that are not considered a high priority for gene editing. Thus, the use of this technology poses various questions regarding its safety, ethics, and social implications. Furthermore, as this technology is in the early stages of development, it is likely that access to this resource will come at a high cost and will not benefit individuals who lack the necessary finances to support such procedures, widening the gap between the socioeconomic classes seen throughout society. A highly controversial use of genome editing is demonstrated when human genomes are altered using technologies such as CRISPR-Cas9 (6). CRISPR-Cas9 involves genome editing that may be used to make changes to genes in egg or sperm cells or to the genes of an embryo that could be passed to future generations. This application of genome editing raises the previously mentioned ethical concern of passing down enhanced human traits such as height or intelligence and the possible issues with the safety of such technique. In addition, it is possible that the use of CRISPR-Cas9 may produce “off-target” effects and can damage the genome in unpredictable ways.
SOURCE: The Scientist
Currently, genomic editing is conducted using genome editing tools to alter or destroy mutated mitochondrial DNA (1). In the embryo, thousands of copies of mitochondrial DNA (mtDNA) are present in the cell’s cytoplasm, which is highly prone to mutations (1). A high enough concentration of mutated mtDNA will lead to the development of mitochondrial diseases, which genomic editing hopes to reduce. This application of genome editing is widely accepted throughout the scientific community; however, it still comes with risks.
Thus, the creation of designer babies remains in the early stages of development. Although there have been many significant advances in genetic editing and modification in recent decades, the topic still causes many to question if it should even exist and the ethical controversies it proposes (5).
References
Pang T.K. Ronald, Ho, P.C. Pang. Designer Babies [Internet]. 2016;26(2): 59-60. Obstetrics, Gynaecology & Reproductive Medicine. Available from: https://doi.org/10.1016/j.ogrm.2015.11.011
Zachary Kazaz—McMaster Integrated Science Program, Specialization in Biology 2025
Recent advancements in genome editing have facilitated major developments in both existing and new gene therapies (Hirakawa et al., 2020). The culmination of these findings became most evident on July 5th 2018, when Dr. Carl June and Professor Michel Sadelain published a seminal review article in the New England Journal of Medicine, reporting the clinical success of chimeric antigen receptor (CAR) T cell therapy against certain haematological cancers; the therapy subsequently received FDA approval for lymphoma and leukaemia treatment (June & Sadelain, 2018). T cells were modified with artificial receptors that associated the recognition of target antigens with the signalling and immunological responses of the T cell (Ellis et al., 2021). Furthermore, genome editing was successfully used to remove immune checkpoints limiting T cell functionality and improving receptor efficacy (Ellis et al., 2021). The successes of CAR T cell therapies have extended the applications of immune cell reprogramming to a population less investigated thus far — the B cell.
Adaptive immune responses are facilitated by white blood cells, or lymphocytes. There are two classes of adaptive immune response: humoral (antibody responses) and cell-mediated responses, primarily enabled by two types of lymphocytes: B-cells and T-cells, respectively (Alberts et al., 2002). Humoral adaptive immunity produces antigen-specific antibodies via B-cells that identify pathogens by binding to their expressed antigens, stimulating cell-mediated immunity by signalling T-cells, cytokines, macrophages and chemical mediators which attack and neutralize the pathogen (Johnson et al., 2018). Thus, B-cells regulate the entire adaptive immune system via general and specific mechanisms, facilitated by cytokine secretion and antigen presentation respectively (Rogers & Cannon, 2021). As a result, B-cells provide a means of modifying holistic immune responses which is a more effective immunotherapy than the sole modification of cell-mediated immunity found in current immunotherapies (e.g., T-cells).
Following the first, primary, response to a specific antigen, the responding, naive, B-cells will proliferate into a colony, differentiate into effector B-cells which produce antibodies, and following infection, will form memory B-cells which encode for and maintain the antigen-specific antibody of the pathogen encountered (Akkaya et al., 2019). This enables more rapid secondary active immune response mobilization if the same antigen exposure occurs subsequently, and can provide lifelong immune surveillance (Akkaya et al., 2019). As a result, humoral immunity facilitated by B-cells is the most capable mechanism of providing prolonged immune surveillance (Rogers & Cannon, 2021).
B-cells possess many unique characteristics that make them a promising focal point for genetic engineering in immunotherapy settings. B-cells can be easily isolated in abundance from peripheral blood, then subsequently activated, grown, and matured in culture ex-vivo (Liebig et al., 2009). It is possible to engineer these isolated B-cells to express a particular gene, mature them into effector B-cells, which produce large amounts of antibodies, and add them back to the host as a remarkably effective form of gene therapy enabling long-term immunity to disease, as seen in Figure 1 (Johnson et al., 2018). In particular, gene editing can be used to alter antigen specificity with a predetermined antibody by means that permit access to all functions of the B-cell during every stage of its life cycle (Rogers & Cannon, 2021).
Figure 1. Diagram displaying the procedure of B-cell immunotherapy in patients using host donor cells (Traxinger, 2019).
By altering the variations of modified antigen-specificity, the response of B-cells to target antigens, their subsequent production of antibodies, expansion, and formation of long-term immunity, we can introduce and evolve long-term antibody specificity to reprogram B-cells that will continue to adapt to their associated pathogens (Rogers & Cannon, 2021). This is particularly relevant, as a majority of current literature on B-cell engineering focuses on producing HIV-specific B-cells (Rogers & Cannon, 2021). The prolonged antibody expression of B-cell therapy can be used to suppress chronic viral infections such as HIV. More importantly, highly mutagenic viruses, such as HIV, are capable of evading antigen-specific antibody responses, and edited B-cells can adapt to these changes, enabling B-cells to keep pace with viral mutations (Ouyang et al., 2017). This is not possible with current therapies that use fixed antigen-specificities.
The broad array of B-cell functions open many potential immune cell gene therapies. For example, the ability of antibody production in effector B-cells allows them to be used as a long-term source for the production of therapeutic proteins in-vivo, such as bnAbs and factor IX to combat hepatitis C virus and HIV (Kuhlmann et al., 2018). Also, it is possible to create these “cellular factories” using stem cells or editing B-cells ex-vivo which can be altered with a variety of methods such as CRISPR/CAS9 and viral vectors which transport the modified gene to loci of interest (Luo et al., 2020). Moreover, naive B-cells can be modified to present antigens and suppress or prevent immune responses to particular antigens, which can be used to combat autoimmune diseases (Scott, 2011).
Interestingly, B-cell engineering offers potential as an improved means of vaccination. In May of 2019, Howell et al. published findings in Scientific Immunology showing that B-cells edited to express antibodies countering respiratory syncytial virus (RSV) produced highly effective and long-lasting protection from RSV infection in mice (Moffett et al., 2019). Such findings convey that sterilizing immunity to pathogens can be accomplished in a more effective manner than current vaccination methods are able to induce or sustain.
Though great strides have been made, moving forwards, many further steps are needed for B-cell therapies to become viable in the future. Up to now, studies have used mice, however, larger animal models more related to human immunology are required to gain more practical insights. Further, studies must be conducted long-term to assess the durability of antibody production and memory in edited B-cells (Rogers & Cannon, 2021). Additionally, novel methods of delivering B-cell therapies to patients must be developed to make B-cells commercially viable and accessible on a broad scale. Engineered B-cells should be manufactured en masse from universally matching batches of unrelated donor cells (i.e. allogeneic) instead of an exclusive therapy manfactured from a single sample of patient-related donor cells (i.e. autologous). Current studies propose using B-cells from induced pluripotent stem cells, which is currently being investigated for use in CAR T cells (French et al., 2015).
Today, genetically engineered B-cells present a great capacity as a highly effective immunotherapy for particular autoimmune disorders, cancers, chronic infectious diseases, and pathogens. Further experimentation is required to progress B-cell gene therapy to human trials, however, in the near future, we are likely to see B-cells accompany CAR T-cells as a novel immune cell therapy. In the far future, the broad and holistic applications of engineered B-cells may become the basis of future immunotherapies, vaccines, and disease treatments.
References
Akkaya M, Kwak K, Pierce SK. B cell memory: Building two walls of protection against pathogens. Nature Reviews Immunology [Internet]. 2019Dec13 [cited 2022Nov29];20(4):229–38. Available from: https://www.nature.com/articles/s41577-019-0244-2
Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Chapter 24: The Adaptive Immune System. In: Molecular Biology of the Cell [Internet]. 4th ed. New York, NY: Garland Science; 2002 [cited 2022Nov28]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK21070/
Ellis GI, Sheppard NC, Riley JL. Genetic engineering of T cells for immunotherapy. Nature Reviews Genetics. 2021Feb18;22(7):427–47. French A, Yang C-T, Taylor S, Watt SM, Carpenter L. Human induced pluripotent stem cell-derived B lymphocytes express SIGM and can be generated via a hemogenic endothelium intermediate. Stem Cells and Development [Internet]. 2015May [cited 2022Dec8];24(9):1082–95. Available from: https://www.liebertpub.com/doi/10.1089/scd.2014.0318
Johnson MJ, Laoharawee K, Lahr WS, Webber BR, Moriarity BS. Engineering of primary human B cells with CRISPR/Cas9 targeted nuclease. Scientific Reports [Internet]. 2018Aug14 [cited 2022Nov29];8(1). Available from: https://www.nature.com/articles/s41598-018-30358-0
June CH, Sadelain M. Chimeric antigen receptor therapy. New England Journal of Medicine. 2018Jul5;379(1):64–73. Kuhlmann A-S, Haworth KG, Barber-Axthelm IM, Ironside C, Giese MA, Peterson CW, et al.
Liebig TM, Fiedler A, Zoghi S, Shimabukuro-Vornhagen A, von Bergwelt-Baildon MS. Generation of human CD40-activated B cells. Journal of Visualized Experiments [Internet]. 2009Oct16 [cited 2022Dec4];(32). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3164064/
Luo B, Zhan Y, Luo M, Dong H, Liu J, Lin Y, et al. Engineering of α-PD-1 antibody-expressing long-lived plasma cells by CRISPR/Cas9-mediated targeted gene integration. Cell Death and Disease [Internet]. 2020Nov12 [cited 2022Dec6];11(973). Available from: https://www.nature.com/articles/s41419-020-03187-1
Moffett HF, Harms CK, Fitzpatrick KS, Tooley MR, Boonyaratanakornkit J, Taylor JJ. B cells engineered to express pathogen-specific antibodies protect against infection. Science Immunology [Internet]. 2019May17 [cited 2022Dec4];4(35). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6913193/
Ouyang Y, Yin Q, Li W, Li Z, Kong D, Wu Y, et al. Escape from humoral immunity is associated with treatment failure in HIV-1-infected patients receiving long-term antiretroviral therapy. Scientific Reports [Internet]. 2017Jul24 [cited 2022Dec4];7(1). Available from: https://www.nature.com/articles/s41598-017-05594-5
Cancer is a leading cause of death globally, accounting for nearly 10 million deaths in 2020, or nearly one in six deaths1. Cancer results from the uncontrollable division of abnormal cells. The most common cancer are breast, lung, colon and rectum, and prostate cancer1. While the survival rate varies depending upon the types of cancer, the chance of survival is significantly greater when cancer is diagnosed earlier. In general, the rate of survival of cancer is 91% when diagnosed at an early stage, and 26% when diagnosed at a later stage7. However, recently scientists have proposed the use of blood tests to diagnose various types of cancer. Blood testing is quick and non-invasive, relatively inexpensive, and readily available. Currently available cancer blood tests include Complete blood count (CBC), CancerSEEK Test, Galleri multicancer early detection (MCED) test and PanSeer Test.
Complete blood count (CBC)
SOURCE: Verywell Health
CBC is a common blood test used to detect a variety of disorders. The results of the CBC can be used to direct one’s diagnosis towards a particular disease2. Moreover, this test can be used to detect Blood Cancers, such as leukemia and lymphoma3.
CancerSEEK Test
SOURCE: Dr. Lal PathLabs Blog
The CancerSEEK Test detects cell-free DNA, cfDNA, and identifies eight biomarkers released by Tumour cells4. This blood test can detect the problems in the early stage of tumor5. Tumors are detected by mutations in genomic positions, such as substitutions, insertions and deletions4. So far, eight types of cancer can be detected with over 99% accuracy, including ovarian, liver, stomach, pancreatic, esophageal, colorectal, breast, and lung4.
Galleri multicancer early detection (MCED) test
SOURCE: Johns Hopkins Medicine Newsroom
The Galleri MCED is a novel, high-performance genomic technology that can detect signals from Cancerous cells at the early stage6. The Galleri MCED test aims to identify cfDNA circulating in the blood, and specifically recognized DNA methylation. The test result can indicate the specific type of cancer, and identify in which organ cancerous cells are present4. There are 12 types of cancer at the early stage that can be detected with 93% accuracy, including anorectal, colorectal, esophageal, gastric, head and neck, hormone receptor-positive breast, liver, lung, ovarian, and pancreatic cancers, in addition to multiple myeloma and lymphoid neoplasms4.
PanSeer Test
SOURCE: Galleri for HCPS
The PanSeer test uses a similar approach to the Galleri MCED test. This test was developed by the Taizhou Longitudinal Study that compared blood samples of individuals with and without cancer. In this study, they compared approximately 400 blood samples with cancer and approximately 400 blood samples without cancer. After that, they record physical measurements and questionnaires about the cancer occurrence, collecting affectional plasma and tissue samples at 3-year intervals7. The test detected patterns of DNA methylation, and 95% of asymptomatic individuals were diagnosed with cancer by using standard detection methods4. However, this test is unable to determine the exact location of the cancer4.
Overall, although blood tests can be used to detect cancer at the early stage which increases the rate of survival, not all types of cancer can be detected. In addition, some confounding factors, such as personal lifestyle, environmental pollution, and individual genetic composition, would make it difficult to develop standardized blood tests for all individuals7.
7. Chen X, Gole J, Gore A, He Q, Lu M, Min J, et al. Non-invasive early detection of cancer four years before conventional diagnosis using a blood test [Internet]. Nature News. Nature Publishing Group; 2020 [cited 2023Jan2]. Available from: https://www.nature.com/articles/s41467-020-17316-z
Cancer refers to any one of a large number of diseases characterized by the development of abnormal cells that divide uncontrollably and have the ability to infiltrate and destroy normal body tissue as well as spread throughout your body.1 It is the second leading cause of death in the world.1 Cancer is caused by mutations to the DNA within cells. These mutations can instruct a healthy cell to allow rapid growth, fail to stop uncontrolled growth or make mistakes when repairing DNA errors.1
Cancer is a highly adaptable disease which causes it to endure the constantly changing microenvironments that its cells encounter2. Cancer cells have a certain degree of adaptive immune resistance, a process in which the cells change their phenotype in response to cytotoxic or proinflammatory immune response9. This response is triggered by the recognition of cancer cells by T cells, leading to the production of immune-activating cytokines9. Cancer cells then hijack mechanisms developed to limit inflammatory and immune responses and protect themselves from the T cell attack9. Because of this process, cancer continues to thwart patients, researchers, and clinicians despite significant progress in understanding its biological underpinnings.3
SOURCE: Future Processing Better Future
As more is learned about the disease itself, more can be learned about how tools can be useful in treatment plans. Currently, artificial intelligence is used in the detection of cancer as it effectively analyzes complex data from many modalities, including clinical text, genomic, metabolomic, and radiomic data (the extraction of mineable data from medical imaging)6. An example of artificial intelligence in cancer diagnosis is imaging tests, which allow your doctor to examine your bones and internal organs in a non-invasive way7. This may include a computerized tomography (CT) scan, bone scan, magnetic resonance imaging (MRI), positron emission tomography (PET) scan, ultrasound and X-ray7.
SOURCE: Stanford Medicine
Artificial intelligence is also used for cancer treatment through something called “precision medicine.” Precision medicine uses specific information about a person’s tumor to help make a diagnosis, plan treatment, and/ or evaluate the effectiveness of treatment5. It involves testing DNA from a patient’s tumor to identify the mutations or other genetic changes that drive their cancer8. Doctors can select a treatment plan that is best suited for that specific patient. Because no two cancers are identical, precision medicine is important as each patient has a unique combination of genetic changes2.
Overall, artificial intelligence provides a gateway to push the boundary of cancer treatment. Currently, it is used most in the detection of cancers through CT scans, bone scans, and PET scans, among others. However, as artificial intelligence is adopted into clinical oncology, its potential to redefine cancer treatment is becoming evident.
3. Linda WB, Hosney A, Schabath MB, Giger ML, Birkbak N, et al. Artificial Intelligence in cancer imaging … – wiley online library [Internet]. American Cancer Society. John Wiley & Sons; 2019 [cited 2022Nov13]. Available from: https://acsjournals.onlinelibrary.wiley.com/doi/full/10.3322/caac.21552
6. Hunter B, Hindocha S, Lee RW. The role of artificial intelligence in early cancer diagnosis [Internet]. National Library of Medicine. U.S. National Library of Medicine; 2022 [cited 2022Nov15]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8946688/
9. Ribas A. Adaptive immune resistance: How cancer protects from immune attack [Internet]. National Library of Medicine. U.S. National Library of Medicine; 2015 [cited 2022Nov25]. Available from: https://pubmed.ncbi.nlm.nih.gov/26272491/
We are very close to a pancreatic cancer vaccine. Indeed, there are currently many clinical trials being conducted that are testing the efficacy of various pancreatic cancer vaccines candidates—some with promising preliminary results.
To provide some background, pancreatic cancer is the fourth most common cause of cancer death in the U.S.3. Pancreatic cancers occur when cells in the pancreas are damaged, causing them to grow out of control3. Current treatments available to treat pancreatic cancer include surgery, chemotherapy, radiation therapy, immunotherapy and dietary changes2. Vaccines that treat cancers, also known as therapeutic vaccines, are a type of cancer treatment called immunotherapy1. These vaccines work to boost the immunity of the patient to fight cancers1.
Figure 1. Image depicting pancreatic cancer. Adapted from the National Cancer Institute9
There are currently many promising clinical trials underway testing vaccines for pancreatic cancer. One of the most successful trials was conducted by Dr. Balachandran in collaboration with the BioNTech company5. They created a mRNA vaccine that targeted neoantigen proteins5. Neoantigens are proteins present on the cancer that alert the immune system of the presence of abnormal development in the body to stop the cancer from spreading5. In 8 of the 16 patients, the vaccine activated T cells of the immune system that recognize the patient’s own pancreatic cancer cells, triggering the immune system to attack the cancer6. There were also delays in the recurrence of pancreatic cancers in these patients5. These findings suggest that T-cell activation of the immune system through the vaccine may have the desired effect of keeping pancreatic cancer in check.
Figure 2. Targeting neoantigen proteins. Adapted from Pearlman et al8
Figure 3. Mechanism for the functioning of cancer vaccines. Adapted from Roy7
mRNA vaccines are created by genetically sequencing the neoantigens proteins in the pancreatic tumors of patients5. The genetic sequences of neoantigens act as a template for making mRNA vaccines. When the vaccine is injected into the person’s bloodstream, it causes the immune cells known as dendritic cells to make the neoantigen proteins5. The dendritic cells train the rest of the immune system to recognize and attack tumor cells expressing the same neoantigen proteins5. Since the immune system is aware of neoantigens as a “harmful protein” to the body, the cancer may have less chance of returning as it is most likely to be destroyed by the immune system5.
Another vaccine developed by Elizabeth Jaffee, M.D., and Daniel Laheru, M.D., is also currently in the clinical trial phase1. This vaccine uses pancreatic cancer cells that are treated with radiation to inhibit their ability to grow1. These cancer cells are also altered genetically to secrete a molecule called GM-CSF1. This molecule attracts immune system cells to the site of the tumor vaccine where they encounter antigen proteins of the radiated cells1. Once these antigens are recognized, this trains the immune system to attack any remaining pancreatic cancer cells in the body1. The mechanism for this vaccine is like that of the mRNA vaccine mentioned above, but the specific proteins and antigen targets that are used differ between the two treatments.
Many other clinical trials for pancreatic cancer vaccines are also currently under development4. These trials include vaccines that are cell based, DNA-based, peptide based and microorganism based4. In summary, many pancreatic cancer vaccines are currently under development at different stages of testing. More clinical testing and FDA approval is required for these vaccines to be commercially available, however the advancements in current vaccinations point to a hopeful future for vaccines to be an effective treatment for pancreatic cancers.
Close your eyes and think of a hospital. What is the first thing that comes to mind? Is it doctors and nurses running around from room to room? Do you think of a hospital drama and your favourite character? Or is it a big and modern building filled with a bunch of high-tech equipment.
It is no secret that hospitals are rely on many types of high-tech equipment to ensure that patients are provided with the best of care. From robots that perform remote concussion evaluations, to proton beam therapy that can be used to treat cancer, to labs that can process over 1,000 COVID-19 tests in a single day, it’s safe to say that technology and healthcare go hand in hand (1). As the largest demographic group in many countries is older adults, hospitals are in constant need of novel and innovative technology to treat them. To top, the increasing number of COVID-19 cases has strained hospital staff and resources, increasing the need for innovative technology.
Medical professionals must ask themselves what piece of technology has such potential to be the key in solving many of these medical problems? What tool has the potential of shaping the future of healthcare?
The answer to this question is 3D printing.
3D printing has come a long way in the last couple decades. It has evolved from a novel and unheard-of tool to a machine that can be found in many hospitals, offices and even homes. Today, 3D printing is used in numerous ways throughout hospitals. For example, it is used to cost effectively print materials such as bandages, stents, casts, and various surgical tools (2)! 3D printing is also used to make prosthetics, lowering the financial burden on patients from tens of thousands of dollars, to only hundreds of dollars. This makes medicine more accessible to many more individuals around the world (3). This amazing tool has also played a major role in supporting hospitals during the COVID-19 pandemic, as 3D printing was used to mass produce additional respirators – a device essential in the treatment of patients suffering from respiratory symptoms associated with severe COVID-19 infection.
Today, many researchers and doctors are looking at 3D printing to bridge the gap between patients requiring organ transplantation and the absence of suitable organ donors. As a result, organ transplantation waitlists can be eliminated, and individuals in need can receive a heart, lung, or kidney. Some researchers are even looking to print tissue, bones, heart valves and much more (4). At the University of Madrid, researchers have begun developing a prototype 3D printer that can print skin, which could potentially be used for accident or burn victims (5). Researchers across the world are pushing the limits of 3D printing every day. With printing costs being much cheaper than acquiring a donated organ, millions of more people may be able to afford such procedures.
At this rate, printing parts of organs is not a question of “if”, but rather “when”. In 2020, the 3D printing market was valued at $12.6 billion, and it is only estimated to keep growing (6). The value of the 3D printing is expected to increase by 17% by 2023, and with it more advances in health care are predicted to follow (6). Time will only tell what will happen to the future of healthcare, but my guess is that 3D printing will play a huge role in it.
Cancer is a disease, resulting from a mutation which causes cells to divide uncontrollably1 and skip cell cycle checkpoints. This results in a tumor, a mass of damaged cells 1left undestroyed. Tumors are classified as either benign or malignant. Benign tumors are not able to spread 1to other regions of the body as they grow. Conversely, malignant tumors can metastasize, spread to other parts of the body as pieces of the original tumor break off and travel through the bloodstream.1 Cancers are predominately categorized as either carcinomas, sarcomas, leukemias or lymphomas, depending on the original cancerous tissue.1
Immunotherapy is a cancer treatment which attempts to boost the immune response of the human body.2 An example of such treatment are cancer vaccines, which administer cancer-specific antigens, molecules for which antibodies are produced, found exclusively on the surface of cancerous cells.2 Personalized cancer vaccines are created using the cancer-specific antigens found on tumor cells of a specific patient.2 Once a patient’s tumor is partially removed during surgery, a vaccine may be tailored using the specific antigens present on the surface of the removed cancerous cells.2
Personalized cancer vaccines contain patient-specific tumor derived epitopes,3 which are regions of the cancer-specific antigens that are recognized by the immune system.4 The immunoresponse to the epitopes is produced by cytotoxic T cells, also known as killer T cells. Cytotoxic T cells are lymphocytes (type of white blood cell) that respond to cytokines and kill cancer cells.5
One type of personalized cancer vaccine is the neoantigen cancer vaccine,3 that uses the specific neoantigens from different mutations of individual patients’ tumors as a component of the vaccine. These neoantigens can be mRNA, DNA, and peptides.3 The synthesis of such vaccines uses next-generation sequencing which maps all the mutations relevant to the patient’s cancer, and gives a neoantigen prediction.3 Then, algorithms and techniques are used to determine which neoantigens3 are specific to the malignant tumors, and which are also present on non-cancerous cells.
Another type of vaccine uses autologous tumor cells, which are cancer cells directly from the patient’s tumor.3 These cells are extracted from the patient, are treated, and then re-administered as either components of cells or as whole cells.3 As a result, autologous tumor cell vaccines contain all the patient-specific tumor-derived antigens, making this type of vaccine faster to produce.3
Personalized cancer vaccines can be injected subcutaneously (under the skin) or intramuscularly (into the muscle), depositing a mass of antigens in the interstitial fluid (fluid surrounding cells).3 The injected antigens are only processed by the immune system once they diffuse into capillary vessels, therefore only a small percentage of the injected antigens are processed.3 As a
consequence, dosage and frequency of administering the vaccine must be increased for the T cell response to be sufficient.3 Therefore, various delivery vectors, including cell vesicles, liposomes, cells and synthetic carriers are used to increase the strength and duration of the immune response.3 Additionally, there are three types of vaccine delivery strategies based on the location of antigen introduction.3 These strategies are LN-targeting (through lymph nodes), intratumoural action (into tumor) and depot-forming (injects vaccine in scaffold to form a depot).3
There are many human clinical trials testing different personalized vaccines. A trial conducted by Moderna and Merck study mRNA-4157, which is in Phase 1.6 The personalized cancer vaccine will be synthesized using the information from specific mutations in 20 neoepitopes to create a single mRNA vaccine that will be injected into the patient.6 Ultimately, personalized cancer vaccines indicate to the immune system which antigens should be targeted, since various malignant tumors have different cell surface antigens.2 The field of immuno-oncology is ever growing with new personalized vaccine types, delivery vectors and delivery methods constantly being tested and researched.
3. Ye T, Li F, Ma G, Wei W. Enhancing therapeutic performance of personalized cancer vaccine via delivery vectors [Internet]. Advanced Drug Delivery Reviews. Elsevier; 2021 [cited 2021 Dec 10]. Available from: https://www.sciencedirect.com/science/article/pii/S0169409X21003203
4. Kogay R, Schönbach C. Epitope [Internet]. Epitope – an overview | ScienceDirect Topics. Encyclopedia of Bioinformatics and Computational Biology; 2019 [cited 2021 Dec 10]. Available from: https://www.sciencedirect.com/topics/neuroscience/epitope
5. Augustyn A. T cell [Internet]. Encyclopædia Britannica. Encyclopædia Britannica, inc.; 2020 [cited 2021Dec10]. Available from: https://www.britannica.com/science/T-cell
Alexia Di Martino—McMaster University Molecular Biology & Genetics 2023
Within our chromosomes, there are billions of nucleotides that are all a part of our genome, the entirety of our DNA. Genomics is the study of the genome. A nucleotide sequence, its precise location, and the gene-gene or gene-protein interactions of specific genes are just a few of the findings that can be discovered through genomics.1 The human body is amazing in its ability to use DNA as a blueprint to direct millions of processes in the body. Of course, our DNA also encodes for the billions of other vital cells – like those of the blood, skin, and brain among other organs – that make up our body on a whole. When cell division goes wrong, though, cells may continue to divide uncontrollably and develop growths that we know as cancer.2
There are two families of genes that influence cancer development. The tumour suppressor gene family has a positive effect on cancerous growth when inactivated or improperly functioning. On the other hand, proto-oncogenes cause cancerous growth when they are mutated and active.3
The Human Genome Project was an advancement in sequencing technology that allowed for a decreased cost of sequencing an organism’s entire genome, as well as improved accuracy of the nucleotides and genes that are sequenced.4 Artificial intelligence and computer algorithms are even further advanced technologies that give researchers the ability to automate pattern-recognition within these sequences. From this, links between a gene’s function in the DNA compared to the patient’s phenotypic presentation of a disease can be made.
Tens of thousands of sequenced genetic mutations have been archived through the amazing work of oncology researchers into genetic libraries. One of these libraries is The Cancer Genome Atlas (TCGA).5 Using a patient’s genome, doctors can refer to these mutated cancer-linked genes to screen patients for susceptibility to a specific cancer.
SOURCE: British Columbia Genome Sciences Centre6
With the knowledge of the patient’s cancerous tumour’s genome, clinicians can identify the exact mechanisms of the cancer cells that causes their proliferation. By comparing the genome of the same patient’s normally functioning ‘germline’ cells to their cancer, researchers can pinpoint the mutated or defective genes responsible for the cancer. They can then recommend better-informed treatments such as pharmaceutical drugs and antibodies targeting certain molecules or pathways of the tumour cells.7 Targeted treatments are much better overall than uninformed therapies. Radiation therapy or stem cell transplants may not be appropriate or as effective in all cases, and can be very expensive. Understanding the genomics of a patient’s cancer could spare them from unnecessarily high medical bills, and more importantly, could have less harmful effects on their body, leading them to being cancer-free more quickly.8
While genomics-driven cancer treatment has been in practice in this way, recent studies into novel gene-editing practices have shown to be promising for the future. In the CRISPR-Cas9 gene editing system, scientists specially design a guide RNA to target a specific DNA fragment. When this guide RNA binds the gene of interest, it associates with a Cas enzyme that cleaves the DNA at that location.9 Scientists may insert a new gene in that cleavage site or perform other modifications depending on their goal.
SOURCE: National Cancer Institute9
Since at least 2017, researchers have been working on using CRISPR-Cas9 on model organisms such as mice and zebrafish in vitro to remove or directly target genes linked to cancer. However, it still poses some challenges when attempting to deliver cancer treatment in vivo.10 These issues are already being studied to create functional and safe delivery of CRISPR-Cas9 gene editing in different tissues in order to accommodate the wide range of cancers seen in patients. As the cancer genome library continues to expand, the CRISPR-Cas9 method of treatment will experience many benefits as well.
The work of biologists in all fields have contributed to this progress – from improved genetic sequencing techniques, to experiments that identify cancer genes, to the assembly of genetic libraries, and everything in between. These advances give every human being a lifesaving advantage in cancer diagnoses. With further research on these gene libraries, scientists will be able to screen the genomes of patients and target cancer-causing genes to inhibit their mechanisms before cancerous cells even get the chance to cause damage.
Mattick JS, Dziadek MA, Terrill BN, Kaplan W, Spigelman AD, Bowling FG, et al. The impact of genomics on the future of Medicine and Health. Medical Journal of Australia. 2014Jul7;201(1):17–20.
Welch JS. Use of whole-genome sequencing to diagnose a cryptic fusion oncogene. JAMA. 2011Apr20;305(15):1577–84.
Zhang H, Qin C, An C, Zheng X, Wen S, Chen W, et al. Application of the CRISPR/cas9-based gene editing technique in basic research, diagnosis, and therapy of cancer. Molecular Cancer. 2021;20(1).
In today’s age, everything from clothing to housing to cars can be customized. We alter things to our liking and do not have to worry about this concept of “one-size-fits-all.” So why should medicine be any different? The emerging concept of precision medicine works to answer this question (1).
In the past, people with the same condition have been prescribed the same drug or therapy with some consideration for factors such as age, sex, weight, or medical history. Despite this, there are still many people for which that medication simply does not work (2). Therefore, we need an approach that specializes treatment for everyone and works by better classifying patients into groups (2).
Precision medicine is much more than matching a blood-type for a transfusion. Precision medicine uses an individual’s genetics, behaviours, and personal environmental factors to create a solution for their healthcare needs (1,3). In medicine, there are always so many external factors that come into play when we prescribe medications or recommend lifestyle changes (3). By gathering information across populations and communities, specific biomarkers can be linked to groups of people, and as a result, be used in targeted treatment or therapy (4). Rather than “personalizing” medicine for any one individual, precision medicine has to do with combining genetics and environments for similar people to find narrowed treatment options that are likely to work and provide optimal benefits (4).
Benefits of such an approach to medicine include higher chances of recovery, as the treatment provided to you has worked for people just like you. Healthcare costs are reduced as treatments are likely to work the first time around (5). Diagnostic equipment use will decline as providers have a reasonable estimate of the issue at hand and can skip directly to specialized technology. A decline in wait times and the process of going from doctor to doctor will follow because your primary provider will have a better idea of where to start and what the problem may be, based on your community or lifestyle. The goal of precision medicine is to get rid of the trial-and-error aspect of medicine to save time, money, and resources. It functions to help people as early as possible in getting treatment and thus recovering (4,5).
SOURCE: EJ Hersom (U.S. Department of Defense)
Precision medicine is attainable because of the rapid data collection available. An attempt to find relationships between biology, lifestyle, and environment has already been put forth by the Obama government starting in 2015 (4,6). All of Us is an initiative under the National Institute of Health (NIH) that is aimed to create a database to find trends in health conditions among people of similar genetics and/or demographics (6). All of Us is a preliminary effort to provide precision medicine to Americans in the near future (6). In addition to efforts set out by the government, the relative speed and low cost associated with genome sequencing today have accelerated the field towards precision medicine (7). Since sequencing now takes a couple of hours instead of a decade, SNPs, epigenetic alterations, and other molecular predispositions can be found and linked to populations (7).
SOURCE: National Institutes of Health
An example that efficiently highlights the potential of this technology is the story of Melanie Nix (8). In 2008, she was diagnosed with triple-negative breast cancer brought about by a mutation on the BRCA gene, a remarkably common condition for many African American women (8). However, through all the research done on this cancer in African American women, statistics showed that Melanie’s best chance was with a bilateral mastectomy (8). Now cancer-free, Melanie also believes that precision medicine allows a mode for preserving one’s health through targeted therapy (8).
SOURCE: Dana-Farber/Boston Children’s Cancer and Blood Disorders Center
It may just be a matter of time until we see this type of precision become a pillar in medicine. The concept of “one-size-fits-all” has been long lost in fashion and lifestyle, and soon may be a staple of all medical practice.
Centers for Disease Control and Prevention. [Internet]. [place unknown]: CDC; [date unknown]. Precision health: Improving health for each of us and all of us. 2020 August 14 [cited 2021 December 8]; Available from:https://www.cdc.gov/genomics/about/precision_med.htm
National Institutes of Health. [Internet]. [place unknown]: U.S. Department of Health and Human Services; [date unknown]. All of us research program overview. [cited 2021 Dec 8]. Available from:https://allofus.nih.gov/about/all-us-research-program-overview
National Institutes of Health. All of Us. [Internet]. [place unknown]: U.S. Department of Health and Human Services; [date unknown] [cited 2021 Dec 8]. Available from: https://allofus.nih.gov/
Gameiro GR, Sinkunas V, Liguori GR, Auler-Júnior JOC. Precision Medicine: Changing the way we think about healthcare. Clinics (Sao Paulo). [Internet]. 2018 [cited 2021 Dec 8];73:723. Available from:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251254/ doi:10.6061/clinics/2017/e723.
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