Emerging CAR landscape for cancer immunotherapy

Abstract

In the last decade, there has been great advancement in manipulating the immune system or the cells of the immune system to bring about effective therapies. While harnessing the immune system against cancer is not a new concept, successful reprograming with T cells with chimeric antigen receptor (CAR) forming CAR-T cell therapy has revolutionized the treatment landscape for patients with refractory, high-grade B cell malignancies. The journey from proof-of-concept to FDA-approved commercial CAR-T products has taken almost 3 decades and untold amount of efforts, resources and manpower. With the success of CD19 CAR adoptive cellular immunotherapy leading the charge, CARs targeting various malignancies are in various stages of active development, racing towards regulatory approval, and raising hopes of further breakthroughs in cancer treatment options. In this review we will highlight recent clinical developments of the B cell maturation antigen (BCMA) CAR-T therapy for multiple myeloma (MM) to showcase how innovative CAR designs, coupled with careful selection of tumor-associated antigens, used in combination with other therapeutic agents, could help overcome some of the current limitations experienced in CAR-T immunotherapy. More patients could benefit from novel upfront cell therapy trials, that when combined with the current established induction regimens could have the potential to recondition and alter tumor environments, help restore somnolent anti-tumor immunity, and induce more effective and durable remissions.

Keywords: BCMA; CAR-T cell therapy; Cell engineering; Cytokine release syndrome; Immunotherapy; Multiple myeloma.