Changing landscape of immuno-oncology: CAR-T therapy and PD1/PDL1 blockade

The current field of cancer treatment is undergoing a revolution. The influx of novel therapies derived from basic research on the immune system has shifted the landscape of modern medicine. Immunotherapy seeks to use the body’s own immune system as a medium to terminate neoplastic cells. This is performed by manipulating the immune system into either targeting cancer antigens or breaking down barriers towards T cell infiltration. The former mechanism uses CAR-T cells as an instrument to target specific cancer neo-antigens. CAR-T cells begin as T cells derived from a patient’s immune system. These cells are removed from the body and engineered to express a chimeric antigen receptor (CAR) through a process of viral transduction. This CAR allows the T cell to recognize and bind to a specific antigen of interest. In most cases, the antigen is present on cancer cells. The T cells, now expressing the CAR receptor, are transplanted back into the body of the patient and proceed to target cancer cells. This therapy has been used in hematological malignancies to great effect. Applying CAR-T cells to solid tumors is an ongoing process, but has been difficult to establish due to the immunosuppressive aspects of the tumor microenvironment. As such, combining CAR-T cells with traditional anti-cancer therapies has been proven to be efficacious in treating patients with solid tumors. In general, immunosuppression is a large problem in the treatment of cancer. Cancer cells and the tumor microenvironment express receptors that downregulate tumor-targeting actions of the immune system. The discovery of the programmed cell death protein 1 (PD1) allowed researchers to create novel antibodies that inhibit immunosuppression. PD1 located on T cells, binds to PDL1 on cancer and stromal cells. This interaction induces exhaustion and anergy in infiltrating T cells, thereby prevent T cells from targeting cancer cells. As such, the newly approved checkpoint blockade antibodies, Nivolumab and Pembrolizumab, block this interaction and allow T cells to carry out their targeting function. CAR-T cells and checkpoint blockade have both seen immense success in clinical trials and are currently being used the clinic. Nonetheless, development of these therapies for different types of cancers is an ongoing process and one that will require immense effort on behalf of the medical and pharmaceutical establishmen