SAFETY AND EFFICIENCY OF CAR-T CELL THERAPY

For years, chemotherapy, surgery and radiation therapy were the generally accepted and used treatments for many cancers including imatinib and trastuzunab drugs that work by slowing or stopping the growth of cancer cells.

Our immune system keeps track of all the substances normally found in the body. Any new foreign substances that our immune system doesn’t recognize either germs or cancer cells will be automatically attacks them as an immune response. But the immune system’s ability to fight cancer is not enough, because sometimes the immune system can’t see the cancer cells as foreign as the cells are similar enough from normal cells.

With this challenge, scientists have been studying of how the immune system will recognize cancer cells and to be stronger that will destroy them. Thus CAR-T Cell Immunotherapy has emerged as what they call the “fifth pillar” or cancer treatment.

CAR-T cell therapy or sometimes called adopted cell transfer therapy is an encouraging new way to get immune cells (T cells) to destroy cancer by modifying and “train” them to attack cancer cells. T-cells are modified in the laboratory by adding a man-made receptor (chimeric antigen receptor or CAR) for a higher chance of identifying specific cancer cell antigen.

In general, different types of immunotherapy may proceed from immune system attacking healthy cells which can cause side effects. Patients undergoing CAR-T cell therapy may have experience serious side effects, especially as the CAR-T cells proliferate in the body to fight cancer cells. This includes neurotoxicity that causes confusion, seizure or severe headaches, serious infections, low blood cell count and weakened immune system.

So far, the most prevalent adverse effect of CAR-T cells is the onset of immune activation or cytokine release syndrome/ CRS. Management of these side effects has become fundamental step in the successful clinical application of CAR-T cells. According to Dr. Kochenderfer, a clinician and translational researcher in the Experimental Transplantation and Immunology Branch of the National Cancer Institute (NCI), generally, patients with the most extensive disease prior to receiving CAR T cells are more likely to experience severe CRS. CRS is considered an “on-target” effect of CAR-T cell therapy. Its presence indicates that active T cells are at work in the body. But these side effects do leave for improvement. Scientists and researchers are hand in hand to improve the safety of this therapy. Since not all T cells are created equal, one way they’re looking at is the standardization of each patient’s dose of T cells and trials suggest that the approach gives better control of dosage and side effects. Also, they have produced caspase-9, a modified version of protein that initiated some CAR-T cells to self-destruct in the body to lessen its side effects.Many clinical trials of CAR-T therapy have shown remission rates for about 94% for severe cancer types. This is promising considering the patients in this trials have not responded to standard treatments.

Recently, Novartis was the first to bring CAR-T therapy in the market called Kymriah, resulted an 83% remission rate for treating B-cell acute lymphoblastic leukemia (ALL). FDA approved Gilead’s Yescarta that have 72% remission rate with patients suffering from aggressive B-cell non-Hodgkin lymphoma, a form of blood cancer. In the success of Novartis and Gilead, other companies are starting their clinical trials with CAR-T therapy.

Even though there are still disputes for this new cancer treatment, we can’t ignore that CAR-T therapy provides hope for the patients. As the therapies are already in the market, it is not bad to expect for a better and more treatments in the future.


References:

(2018). Retrieved from https://labiotech.eu/car-t-approval-fda-novartis-kymriah/https://labiotech.eu/car-t-approval-fda-novartis-kymriah/

CAR T Cells: Engineering Immune Cells to Treat Cancer. (2018). Retrieved from https://www.cancer.gov/about-cancer/treatment/research/car-t-cells

What Is Cancer Immunotherapy? | American Cancer Society. (2018). Retrieved from https://www.cancer.org/treatment/treatments-and-side-effects/treatment-types/immunotherapy/what-is-immunotherapy.html

World Best Ever CAR-T Results have Just been Disclosed. (2018). Retrieved from https://labiotech.eu/world-best-ever-car-t-results-for-cancer-have-bust-been-disclosed/

Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188-195. (2015). Blood, 126(8), 1048-1048. doi: 10.1182/blood-2015-07-656918

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