Augmented Human Starts With Augmented Immunity
The Tale of Cancer Immunotherapy — Properly trained, our immune system can beat any disease.
Our immune system is well-known for protecting us from foreign invading forces of pathogens and germs. It also maintains peace and balance within the body. It is made up of specialized “soldiers” with names like dendritic cells, T cells, B cells, monocytes, neutrophils and macrophages. After their development in the thymus and bone marrow, they move to reside in the lymph nodes and spleen. These immune cells travel around the body and scout our tissues and organs for signs of anything out of ordinary. One of their notable functions is to monitor for the presence of damaged DNAs or rapidly dividing cells gone out of control that may lead to disastrous outcomes like cancer.
The immune function can be divided into the innate and adaptive immune systems. The former’s responsibilities cover the surface of the body or airways in the lungs to provide immediate, short term protection. In the instance when there is danger, it alerts the adaptive immune system for backup.
T cells are the cells of the adaptive immune system tasked to kill cancerous (rapidly dividing out of control) cells. Dendritic cells educate these T cells to recognize the presence of cancer. This ‘education’ is highly effective because of the specific receptors on the T cell surface that takes in pieces of the cancerous cells ripped off by Dendritic cells to help them differentiate better. It’s like training a dog to find somebody by sniffing that person’s scent off his/her belongings.
This understanding of the immune system has led to new immunity-based cancer treatments. Immunotherapy or immune-oncology is a form of cancer treatment unlike other primary pillars of interventions such as chemotherapy, surgery or radiation therapy. This treatment method is highly specific and personalized, capable of harnessing the power of the patient’s own immune system to kill cancerous cells with minimal collateral damage to other healthy living cells.
Types of Cancer Immunotherapy:
Following are the various types of cancer immunotherapy:
1. Checkpoint inhibitors
2. CART-T cell therapy
3. Oncolytic viruses
4. Cancer vaccines
1. Checkpoint inhibitors:
There are proteins or “weapons” that cancer uses to protect themselves from harm, a few of them are known as CTLA-4 inhibitors, PD-1 inhibitors and PD-L1 inhibitors, they interact with T cells and inhibit their function. As a result, cancerous cells continue to grow and spread in the body. To remove this cancer defence mechanism, a type of medicinal drug known as checkpoint inhibitors are used as a type of cancer immunotherapy. They are also known as checkpoint blockade drugs due to their ability to block those inhibitory proteins that cancer uses as defensive weapons, thus allowing the T cells to destroy them.
2. CAR-T cell therapy:
One of the major problems in using our immune system to fight cancer is: what if there isn’t anything on the cancer cell surface for our “soldiers” to recognize and kill? Remember, cancer cells are our own cells, they simply turned rebellious and revolted. They still carry the attributes of our healthy cells in almost every way, so we must find a way to isolate them. So this is where smart biomedical scientists came in, and there is a technique that has been in development for decades. Researchers figured out the ways to engineer the T-cells by expanding in the laboratory and giving them a new receptor that helps these cells to recognize and activate T cells. This method is called chimeric antigen receptor T (CAR-T) cell therapy. CAR-T cells can be injected into the body without any adverse responses from the host (they were ‘augmented’ or engineered from the host’s T-cells, thus going for the search and destroy mission once again, knowing what to look for this time.
3. Oncolytic Virus Therapy:
These are other ways that biomedical scientists have figured out to educate the T cells and train them with the enhanced ability to kill cancerous cells. A method takes advantage of the aggressiveness and attack efficiency of viruses to target cancerous cells. We all know how good the viruses are at infecting our systems, just think that we still haven’t found a way to stop the common cold and flu yet. So the rationale of re-purposing them for cancer sounds like a great idea! Oncolytic viruses or modified viruses are the outcomes of this research and they have been successfully engineered in labs. Their usual harmful teeth were taken out, hence no harm can be done to us, and replaced with cancer-specific ones. After placing into the body, they leverage their ability to search and break down target cancer cells. The lysed cancer cells cause the release of some molecules such as tumour associated antigens (TAAs) that also activate the T cells to kill other cancer cells as well. In this way, oncolytic viruses work synergistically with T-cells to recognize and destroy cancers.
4. Cancer vaccines:
At this point, everyone is familiar with the term vaccine, some with good feelings about it, some may not. Regardless of the political chaos that it has caused in the world, it is really a medically and scientifically sound approach to equip our bodies to fight off dangerous pathogens. Our modern society is able to last this long, this healthy to this point, is largely due to the marvel vaccine inventions that has eliminated the occurrence of devastating infectious diseases like Polio, Tetanus, Hepatitis B, Rubella, just to name a few that you may have forgotten. They are no longer a threat because of mass inoculation, thanks to vaccines. Cancer acts like an infection, growing out of control, perhaps we can develop a vaccine-like treatment to target and prevent it?! It is the idea behind cancer vaccines, let’s use it to help educate the T cells to recognize and eliminate cancer cells. They can be prepared by extracting pieces from cancer cells, called antigens. Then supplying these non-harmful antigens to the body. T cells can now recognize these antigens picked up by dendritic cells. As a result, T cells get activated, return to cancer and bring on destruction.
There is a delicate and more personalized approach to cancer vaccines. It is called Neoantigen vaccines. It takes advantage of the mutations in a patient’s tumours. In this personalized therapy, DNA is sequenced and the mutations that make the tumours different from the rest of the patient’s healthy cells are identified. Those mutations are incorporated into a vaccine so that the immune responses to those specific antigens can be boosted. These neoantigen vaccines will only work for a specific patient, and not for everyone.
Immunotherapy for Mutated Cancer Cells:
Immunotherapy is more effective for mutated cancer cells because immune cells are better at recognizing cancer cells when there is more distinction in cancer compared to healthy cells. For an instance, Microsatellite instability (MSI) is a mutation that scientists have discovered that makes cancer mutate rapidly. In a way, it actually makes cancer cells more sensitive to immunotherapy because they are like walking targets dressed as clowns for the immune system. Another mutation known as TMB which stands for tumour mutational burden acts as a genomic biomarker that measures and predicts a patient’s response to immunotherapy. Based on this response, the methods of immunotherapy can be improved and made more effective against cancer aggressions.
Role of the Microbiome in Cancer Immunotherapy:
The microbiome is the bacteria that reside on or within human tissues. We have billions of beneficial bacteria living in peaceful harmony in our gut that help to digest food, exact vital nutrients and maintain over 70% of the immune system. Their diversity and quantity vary in everyone depending on the foods that you consume, lifestyle practices, and other factors. However, food consumption has the largest influence on this innate ecosystem which produces so many benefits for the body. Therefore eating a balanced whole food diet such as a diet rich in fibre, fruits, vegetables, and legumes, can significantly improve your ability to respond to immunotherapy.
Side effects of Immunotherapy:
Nothing is without side effects. But it is all relative. Compared to the traditional interventional strategies (chemo, radiation, surgery, etc.) used by oncologists and surgeons for ages, immunotherapy seems to be a much more “logical” approach (help the body heal itself). The side effects don’t appear in all patients and hinge on the technique used and responses in a particular patient. Depending on the type of cancer, location of the tumour, health of the patient, etc., the most common side effects associated with cancer immune therapy include autoimmune consequences in which the immune system starts to recognize and destroy your own tissues and organs. You can also develop resistance to immunotherapy because whenever you apply pressure on the biological system, the system evolves around the pressure.
Promises of Cancer Immunotherapy:
Cancer immunotherapy is a highly promising alternative approach to treating cancer. Major pharmaceutical companies, not simply academic laboratories are actively researching to strengthen this method’s ability in destroying cancer with minimal side effects. In the future, cancer immunotherapy will be more effective with the following advancements in ongoing clinical research:
Biomarkers are the things that we can measure in blood to tell whether a patient is responding to immunotherapy or not. Immunotherapy can be made more effective by discovering and validating new biomarkers.
We can combine multiple types of immunotherapies such as Combining PDL-1 with CAR-T to boost the immune system against cancers.
Research is ongoing to provide vaccines and remove the checkpoints that are keeping the tumours protected from the T cells.
Clinical trials are focusing on minimizing any of the off-target or side effects from immunotherapy. In this way, more patients will be treated by immunotherapy.