CAR-T, A Promising Future

For many years the pillars of cancer treatment were surgery, chemotherapy, and radiation therapy. Soon, targeted therapies began to emerge such as Gleevec® and Herceptin®. Targeted therapies are those that target specific molecular elements primarily in cancer cells.

Even more recently, immunotherapy has been getting a lot of attention. Immunotherapy is used to strengthen the patients immune system to allow it to attack tumors. A more rapidly emerging immunotherapy is called adoptive cell transfer (ACT). ACT involves collecting and using the patients’ own immune cells to treat their cancer. This article is going to focus on one of the more successful ACT treatments called CAR-T therapy. CAR-T has gained the spotlight as it is being used in small clinical trials to primarily treat patients with advanced blood cancers and seen excellent results.

The backbone of CAR-T therapy is T-cells. T- cells are responsible for directing the immune response and killing host cells infected by pathogens. The therapy includes taking the patients blood and separating the T-cells out. Using a disarmed virus, most commonly lentivirus (HIV), the T-cells are genetically engineered to produce specific receptors on their surface called chimeric antigen receptors (CARs). The receptors allow the T-cell to recognize a specific protein, or antigen on tumor cells.

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The FDA approved CAR-T therapy for treatment of refractory and previously treated with remission ALL in children and adolescents in August 2017. One of the earlier trials using CAR-T CD19 modified T-cells saw 27 out of the 30 patients have a complete response in that all signs of cancer disappeared with many of the patients continuing to show no signs of remission. CD19, also called B-lymphocyte antigen CD19 is a protein that is encoded by the CD19 gene and found on the surface of B-cells. B-cell ALL is the predominant pediatric ALL.

Because of the strong results seen in using CAR-T to treat ALL, there are ongoing trials exploring the therapy in different lymphomas. On October 18th, 2017 the FDA approved Yescarta™ from Kite Pharma for the treatment of large-B-cell lymphomas based on the results of a large trial that was funded by Kite Pharma.

The rapid advances and growth within CAR-T therapy has given hope and another treatment option to those who have undergone standard regimens of treatment unsuccessfully.

There are efforts to expand the use of CAR-T for the treatment of solid tumor cancers. These efforts have been largely unsuccessful as it is increasingly difficult to identify unique antigens on the surface of solid tumors. There is ongoing research into other forms of ACT that may be better suited to treat solid tumor cancers.

There is an ongoing ethics battle as Novartis the owner of the FDA approved CAR-T therapy tisagenlecleucel (Kymriah®) set the price for a single infusion at $475,000. Novartis claims that the cost-effective price is between $600,000-$750,000, but recognize the importance of the therapy, thus the lower price set. ACT therapy is in its infancy, with CAR therapy exploding as more and more research is done. Its hard to understand pharmaceutical companies position as the high price tag may keep the drug out of the hands that may need it the most. People fail to understand that a stem cell transplant on average costs anywhere from $500,000-$600,000, not to mention the accumulation of previous chemotherapy and radiation regimens.

With the discovery of ACT and CAR-T comes a paradigm shift within cancer treatment that is now only showing its true potential. There is much more to be discovered and much more to understand.

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