According to the world health organization, Cancer is the second leading cause of death globally and accounted for 9.6 million death in 2018. Lung, prostate, colorectal, stomach and liver cancer are the most common types of cancer in men, while breast, colorectal, lung, cervix and stomach cancer are the most common among women (WHO, 2017).
National expenditures for cancer care in the United States totaled nearly $125 billion in 2010 and could reach $156 billion in 2020. The number of new cancer cases will rise from 14 million to 22 million within the next two decades. It is expected that the USA national expenditure of Lymphoma only is 16-20 billion USD per year
For years, the foundations of cancer treatment were surgery, chemotherapy, and radiation therapy. Over the last two decades, targeted therapies like imatinib (Gleevec®) and trastuzumab (Herceptin®), drugs that target cancer cells by homing in on specific molecular changes seen primarily in those cells have also cemented themselves as standard treatments for many cancers. But over the past several years, immunotherapy therapies that enlist and strengthen the power of a patient’s immune system to attack tumors has emerged as what many in the cancer community now call the “fifth pillar” of cancer treatment.
A rapidly emerging immunotherapy approach is called Adoptive Cell Transfer (ACT): collecting and using patients’ own immune cells to treat their cancer. There are several types of ACT such as Tumor Infiltrating Lymphocytes (TILs), engineered T Cell Receptor (TCRs), Chimeric Antigen Receptor T cell (CAR-T) and Natural Killer cells (NK). The first CAR T-cell therapy was approved in August 2017 for the treatment of children with acute lymphoblastic leukemia (ALL) by Novartis Pharma. The second, for adults with advanced lymphomas, approved in Oct 2017 (Kite Pharma) with basically the same therapy (CAR T against CD19). Only a little over 100 patients with large B-cell lymphomas were enrolled in the trial that led to the approval. All patients in the trial had advanced disease that was progressing after they had received at least two previous treatments. Approximately 20% of the patients had already undergone a stem cell transplant. Approximately half of the patients had a complete response to the treatment, that is, their cancer disappeared completely. And nearly 30% of patients had a partial response, some reduction in the extent of their disease. In general, over 80% showed a response to the treatment with about 50% complete response. This led to an unprecedent approval of the therapy after phase 2 only for both companies.
Novartis has set the price per treatment initially at about $650,000 USD but due to public pressure they recently announced that the market price per batch will be $475,000 USD. Kite Pharma announced recently that there per patient price will be $375,000 USD. The cost of goods manufactured including labor are estimated at ~$150,000 USD per dose.
Another emerging immune cell therapy for cancer is called Tumor Infiltrating Lymphocyte (TIL). The treatment involves the large-scale expansion of TIL (containing T cells) in vitro from tumor specimens followed by infusion of the expanded cells into the patient together with Interleukin-2 (IL-2) as a growth factor. These expanded TIL are infused into cancer patients where they home into and attack tumors. TIL therapy has been shown to be highly successful at eradicating large refractory tumors in greater than 50% of treated melanoma patients at the National Cancer Institute (NCI) in Bethesda, MD. One of the main drawbacks of this therapy is the long, labor intensive manufacturing process and the high dosage that are needed for treatment. The NIH published treatment cost for clinical trials are currently $500,000 USD.
Natural Killer (NK) cells are cytotoxic immune cells with an innate capacity for eliminating transformed cells in a non-major histocompatibility complex (MHC) and non-tumor antigen-restricted manner. Different strategies have been developed using NK cells to fight cancer including CAR NK and NK combined with immune therapy. Recent clinical trials have shown impressive and processing response of cancer patients to NK treatments.
T Cell Receptor (TCR) therapy is another type of immune cell therapy similar to CAR T, in which instead of an engineered T cell receptor the transduced receptor is a native tumor T cell receptor. The main advantage in this therapy is its minimal toxicity as the T cell still maintains its natural “controls” leading to higher safety profile. The manufacturing profile and costs are similar to
Photographer: Bar Gutharts