This should be the most exciting technology in the field of oncology treatment in 2014. At the American Clinical Oncology Annual Meeting in June, Novartis’ partner Professor Tanaka of the University of Pennsylvania gave a keynote presentation in which he used CAR-T technology targeting CD19 to treat relapsed acute B-cell leukemia with a complete remission rate of 90%, and for chronic B-lymphatic leukemia (CLL), it had a complete remission rate of 87%. These two figures are significant in the field of oncology treatment.
CAR-T is somewhat similar to the prevalent CIK technology in China, in which lymphocytes are extracted from the patient’s body and then a gene (called CAR if the gene is derived from an antibody and TCR if it is derived from a TCR) is transfected into it with a virus, and this gene encodes a specific antibody recognition region against a specific tumor antigen. In simple terms, it is adding a pair of eyes to the lymphocytes so that they can see the tumor cells, and then these lymphocytes can specifically kill the tumor. So far, clinical trials of CAR-T technology for leukemia have been very effective, but because it involves the transfusion of large numbers of active immune cells back into the body, there are significant side effects, such as fever. The concern is that a side effect called cytokine secretion syndrome (CRS) can occur. The good news is that we have specific treatment for this side effect, but this treatment must be done under strict physician supervision.
CAR-T technology faces two challenges: one is the specificity of target selection, the eyes that guide the T cells to kill tumor cells. This pair of eyes must be specific, otherwise they will attack normal cells and cause unpredictable side effects; one is the effect of CAR-T on solid tumors. CAR-T is very effective in treating leukemia, which is in the blood, and there is no problem of suppression of immune cells by the tumor microenvironment. However, this is not the case with solid tumors, which have their own specific microenvironment, an environment that suppresses the T cells that kill them, including, of course, CAR-T cells. a 2013 CAR-T article using mice as a model has shown that CAR-T cells also highly express PD-1, a suppressor molecule. Of course, there is a solution, which is to use PD-1 antibodies together with CAR-T in the hope of unlocking the microenvironment’s inhibition of CAR-T cells. So, the PD-1 antibody is very significant in that it works well on its own and may have a 1+1>2 effect when used together with other treatments.