GLOBAL CHIMERIC ANTIGEN RECEPTOR (CAR) T CELLS THERAPY AS CANCER ANTIDOTE

Cancer is one of the most dreaded disease, with very high mortality rate. Though treatments like radiation therapy and chemotherapy are available, these tend to destroy not only cancerous cells but also the healthy ones. CAR cells therapy scores over them since it specifically targets the afflicted cells without harming the healthy ones. CARs are receptor proteins which are generally engineered to produce an artificial T-Cell receptor used in this immunotherapy. Patient’s T-cells are isolated from his blood and Chimeric T Cell receptors are injected to give T cells the neo ability to target a specific protein. The receptors are chimeric since they have the dual capability of binding antigen and activating T cell in a single receptor. Once active, these cells become cytotoxic and proceed to destroy cancerous cells, through multiple routes. These cells are grown in the lab and then infused in the patient’s body. Once infused they act as a living drug against cancer cells. This is a promising treatment since CAR modified T-cells can be engineered to target associated antigen. There is a great potential of this cancer therapy.

There are multiple factors that seem to suggest that there is a growing opportunity in this market for cancer treatment. Some of these drivers are:

First, technological advancement: Many new drugs to treat the menace of cancer have been approved by respective regulatory bodies. In addition, many treatments are at varied stages of clinical trials to assess their efficacy in treating the disease. Axicabtagene, Tisagenleeleucel, and some more are the CAR T cell-based treatments approved by the US FDA. Glioblastoma is being used to target ECFR VIII. There are also efforts underway to engineer CAR targeting other blood cancer antigens in Hodgkin’s lymphoma, BCMA in multiple myeloma, CD33 in acute myeloid leukemia, and so on. This therapy is also being used for life threatening cytokine release syndrome (CRS). This therapy is also employed to treat pancreatic cancer. Number of such patients is growing.

As of March 2019, an estimated 364 clinical trials were on globally relating to CAR-T cells. CD19 is the most popular antigen target, and most of these trials were aimed at finding treatment of blood cancer, one of the most dreaded disease. Admittedly, solid tumors have presented themselves as a more difficult target; in this case identification of good antigens has not been easy, since the hostile tumor microenvironment suppresses T cell activity.

Another factor to keep in mind is that although the initial clinical remission rate after one undergoes the CAR-T cell therapy is nearly 90%, long term survival rates are not that promising, since newly emerged leukemia cells may evade recognition by the CD19 infused CAR-T cells. But preclinical trails developing CAR-T cells with dual targeting – CD19 plus CD22 – have shown some promise.

Finally, increasing FDA approvals have culminated in the launching of newer and technological more advanced cancer treatments; this will surely boost the global market growth.

Second, growing prevalence of cancer globally is another stimulant. Cancer can affect and attack any body part – lung, lever, pancreas, breast or blood. Nearly 1.7 million new cases of cancer were diagnosed and about 6 lakh deaths were reported in the US in 2018 alone. Increasing number of cases are also being reported from countries like India, US and whole of Europe. These are many reasons for growing occurrence and prevalence of cancer, including smoking and intake of excessive alcohol. Another important contributor has been obesity right from childhood due to unhealthy food habits. All these cases can be treated through CAR-T cell therapy. If we take India as a case study, according to WHO, 1.16 million new cancer cases were likely to be reported in 2018 and more that 50% of these will be in women. Cancer is the second biggest killer in India; out of the total, 8.17% deaths (2018) occurred in India alone. Worldwide 9.6 million were estimated to die of cancer in 2018. No doubt these figures are very depressing but then there is a ray of hope for them in CAR-T cell therapy. This points towards further fueling up of demand for such therapy.

Third factor is the overall growth of Pharma industry. Owing to growing incidences of various ailments, including cancer the healthcare and Pharma companies have smelled the opportunities that are open for exploitation, even if confronted by strong challenges. They have engaged themselves successfully in development of innovative, effective and efficient immune treatments, including the development of cell therapy. This has boosted the fortunes of this industry. As noted above lack of exercise, sedentary lifestyle, increasing intake of toxic products like tobacco and alcohol, unhealthy food habits, obesity, and last but not the least growing menace of pollution – all these factors have been contributing towards making cancer like an epidemic. The patient population and consequent number of deaths are swelling. So well equipped and competent companies like Pfizer and Novartis have actively engaged themselves in finding innovative solutions through CAR T- cell therapy. Indeed, since the ROI in pharma industry is very promising, the biotech, pharma, and healthcare companies in general are spending huge dollars on discovering new pharmacopic products, including the global CAR T cell therapy. Medical research in U.S., Europe, and even developing countries like India and China are demanding and getting attractive dollars sums.

Treatment of cancer-a disease in which abnormal cells divide uncontrollably and destroy body tissues- can ofcourse come in the form of surgery, radiation therapy, chemotherapy, immunotherapy, harmone therapy, and of course targeted therapy. CAR-T cells treats cancer by targeting the changes in cancer cells through antibodies. Presently fourth generation CARs (known as TRUCKS) are available which have added factors that enhance T-cell expansion, persistence, and anti-tumoral activity. To these engineered T cells can be added a synthetic control mechanism which will ensure a control of, and continuation of activity of these cells in the patient’s body, with a further aim of reducing toxic side effects. The CAR T cell therapy is truly a futuristic treatment which in many way scores over other forms of cancer removal reduction techniques.

Ofcourse as of now there remain challenges. Thus, first there exists an inability to control the rate of cytokine release and tumorlysis. Second, there exists a need to generate a different CAR T cell for each unique tumor antigen. But research is going on to take care of these shortcomings, For example the second issue may be resolved using the adaptor approach. All in all the future is very promising       



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Contributed by: Prof. K.K. Srivastava
KKS is an academic, author, writer, researcher, and corporate speaker. He writes regularly on Economics, Management, Technology, and others areas.



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