Current modalities in cancer immunotherapy: Immunomodulatory antibodies, CARs and vaccines

Successes of immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cell therapy in curing patients with otherwise lethal cancers have validated immunotherapy as a treatment for cancer and have inspired excitement for its broader potential. Most promising is the ability of each approach to eliminate bulky and advanced-stage cancers and to achieve durable cures. Despite this success, to date only a subset of cancer patients and a limited number of cancer types respond to these therapies. A major goal now is to expand the types of cancer and number of patients who can be successfully treated. To this end a multitude of immunotherapies are being tested clinically in new combinations, and many new immunomodulatory antibodies and CARs are in development. A third major immunotherapeutic approach with renewed interest is cancer vaccines. While over 20 years of therapeutic cancer vaccine trials have met with limited success, these studies have laid the groundwork for the use of therapeutic vaccines in combination with other immunotherapies or alone as prophylactic cancer vaccines. Prophylactic vaccines are now poised to revolutionize cancer prevention as they have done for the prevention of infectious diseases. In this review we examine three major cancer immunotherapy modalities: immunomodulatory antibodies, CAR T cell therapy and vaccines. For each we describe the current state of the art and outline major challenges and research directions forward.