Most people must have heard revolutionary cancer therapy called CAR-T cell therapy, a kind of cancer immunotherapy. It has changed the landscape of cancer therapy and has the potential of curing some of the chemotherapy refractory blood cancer such as acute lymphoblastic leukemia (ALL).
Cancer immunotherapy is not a very new science, but it is the culmination of cumulative knowledge gained through countless experiments in immunology and cancer. In 1893, William Coley's observed reduction in tumor size upon injection of streptococcus bacteria. Giving BCG vaccine in early stage of bladder cancer is a form of oldest cancer immunotherapy which is still used in clinical practice.
T cells are the type of a white blood cell which plays an essential role in mounting an appropriate immune response to either diseased cells (virus-infected or cancer cells) or foreign pathogens. Cytotoxic T cells are central in killing cancerous cells. They recognize cancer cells through a particular receptor called T cell receptor (TCR) which binds to the novel antigen expressed only on cancer cells and thereby killing them. However, cytotoxic T cell which can recognize unique tumor antigen is scarce in number, or sometimes tumor itself create microenvironment to decrease their frequency around the tumor microenvironment. One way to overcome this challenge is to engineer T cells ex-vivo isolated from either blood of the patient or healthy individual. In this method, T cells are engineered to produce a single chain variable fragment of an antibody (chimeric antigen receptor; CAR) which recognizes unique antigen only expressed onto tumor cells, e.g., CD19 in case of ALL. They are expended in large number ex-vivo and injected into the patient, where further proliferation produces more engineered T cells specific to tumor cells. Expended CAR-T cells lead to complete killing of all tumor cells without harming healthy normal cells, unlike conventional cancer treatment where most of the side effects come from the killing of healthy cells. However, there are some challenges associated with CAR-T cell therapy such as cytokine storm and expensive nature of its production. Moreover, they are not currently suitable for solid tumors which constitute the majority of cancer found among the population.
FDA has recently approved two CAR-T cell therapy based on CD19 chimeric antigen receptor to treat ALL and diffuse large B cell lymphoma.