Chimeric Antigen Receptor T Cells: A Race to Revolutionize Cancer Therapy

Abstract

For years, cancer treatment was dominated by chemotherapy, radiation therapy, and stem cell transplantation. New insights into genetic characteristics of leukemic cells have initiated the development of the chimeric antigen receptor (CAR) T-cell therapy. This type of adoptive cell immunotherapy has been a breakthrough in the treatment of aggressive B-cell lymphoma and B-cell precursor acute lymphoblastic leukemia. In August 2018, the European Commission has approved the first CAR T-cell products – tisagenlecleucel (Kymriah®, Novartis) and axicabtagene ciloleucel (Yescarta®, Gilead) – for hematological neoplasms in Europe. As CAR T cells are a living drug, its benefits can last for many years. The administration of CAR T cells is a complex and costly endeavor involving cell manufacture, shipping of apheresis products, and management of novel and severe adverse reactions. The most common toxicities observed after CAR T-cell therapy are cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. Current research focuses on improved safety and efficacy in hematological malignancies as well as the translation of CAR T-cell therapy to solid tumors. This review covers the development and current status of CAR T-cell therapy in a clinical setting with focus on challenges and future opportunities.

Beyond thrombosis: the impact of tissue factor signaling in cancer

“…A rapidly emerging immunotherapy strategy for treating cancer is chimeric antigen receptor (CAR)-modified T cells (CAR T) [ 207 , 208 ]. To date, CAR T therapy against hematopoietic cancers has met with some success [ 209 ], but whether it has real potential against solid tumors is debatable.…”

Gene modification strategies for next-generation CAR T cells against solid cancers

“…Owning to these results, Kymriah, a CAR T therapy developed by Novartis, has been approved by the US Food and Drug Administration (FDA) and the European Commission for the treatment of relapsed or refractory acute lymphoblastic leukemia in children and young adults. In October 2017, the US FDA permitted Yescarta, another CD19-targeting CAR T cell product, to treat relapsed or difficult-to-treat large B cell lymphoma [7,8].…”

Adapter chimeric antigen receptor (AdCAR)-engineered NK-92 cells: an off-the-shelf cellular therapeutic for universal tumor targeting

“…2 Currently, all FDA-approved CAR products are second-generation CAR T cells used to treat a variety of high-grade or refractory hematological malignancies. 4,[7][8][9] Despite the recent clinical success of CAR T cell therapies, several obstacles and challenges remain.…”