In the past two months, the FDA has approved a revolutionary new form of immunotherapy, called chimeric antigen receptor (CAR) T cell therapy, for two blood cancers: B cell acute lymphoblastic leukemia (ALL) in August, 2017 and now on October 18th, for aggressive diffuse large B cell lymphoma (DLBCL), a type of non-Hodgkin lymphoma.
The new immunotherapies are for patients who have not responded to or have relapsed twice after available standard treatments. Kymriah is specifically for the pediatric population and patients up to 25 years of age with ALL. Yescarta will specifically treat adults with DLBCL and several other types of B cell non-Hodgkin lymphoma.
Immunotherapies are a class of cancer treatments designed to strengthen the ability of the patient’s own immune system to fight cancer, and kill cancer cells, versus using synthetic molecules (drugs) or radiation to directly target cancer. CAR T-cell therapy is an adoptive cell transfer (ACT), where the patient’s own immune cells are collected and used to treat cancer.
In CAR-T treatment, receptors are used to graft the specificity of a monoclonal antibody onto a T cell. The T cells are removed in the ACT process from the body, and modified such that they express receptors specific to the patient’s particular cancer. When reintroduced to the body, the T cells then target cancer.
Currently, CAR-T therapies have been effective in B cell cancers or lymphomas, a type of blood cancer of the immune system’s B cells, which make antibodies to fight infectious agents. In this case, T cells are engineered to target a protein on B cells, and kill those cells. While some healthy, non-cancerous B cells are also killed, most patients can live without these B cells or get intravenous immunoglobulin as a replacement.
“The results in blood cancers have been pretty remarkable, but in solid tumors, it’s not clear that this therapy, the way it’s designed now, is going to be enough,” according to Dr. Marcela Maus, director of cellular immunotherapy at Massachusetts General Hospital.
Research, however, is demonstrating there is hope yet that these blood-borne cancer immune therapies will successfully be used to battle solid tumors. National Foundation for Cancer Research (NFCR) sponsored scientist, Wayne Marasco, M.D., Ph.D., of Dana-Farber Cancer Institute and Harvard Medical School, is advancing his research on CAR-T cells to treat metastatic clear cell renal cell carcinoma (ccRCC), the most common type of kidney cancer.
These CAR-T cells express an antibody to CAIX, an antigen on the cancerous kidney cells but not on normal cells, allowing the CAR-T cells to home in to the tumor. Secondly, to counter attack the negative tumor microenvironment, the CAR-T cells are empowered to secrete anti-PD-L1 antibodies to bind to PD-L1 antigens in the milieu. The anti-PL-L1 antibodies will combat ‘T cell exhaustion’ — T cells that have become dysfunctional by upregulating their PD-1 receptors to bind to PD-L1. T cells will then be unleashed to fight a more rigorous attack against the cancer. This innovation should provide renewed potential for CAR-T immunotherapy of solid tumors.
Perhaps the biggest challenge of making CAR-T treatment accessible to the masses is its cost. The one- time treatment with these two new drugs is high: Kymriah is priced at $475,000, and Yescarta, Gilead’s new therapy for DLBCL, will cost $373,000.
There are currently 16 sites authorized to offer Yescarta including Dana Farber, Mass General, the Mayo Clinic, Memorial Sloan Kettering, MD Anderson, Stanford Health Care, Vanderbilt Medical Center, Moffitt Cancer Center, the University of Chicago, the University of Kansas Cancer Center, the Barbara Ann Karmanos Cancer Institute, Siteman Cancer Center, The Ohio State University Comprehensive Cancer Center, the Seattle Cancer Care Alliance, the Sylvester Comprehensive Cancer Center, and City of Hope. Kymriah is only available at select treatment centers. For more information, call the REMS Center at 1-844-4KYMRIAH. (1-844-459-6742).