Jokūbas Liutkus¹, Dalia Zykutė¹

¹Lithuanian University of Health Sciences, Medical Academy, Faculty of Medicine, Kaunas, Lithuania.

Abstract

Chimeric antigen receptor (CAR) T cell therapy is at the forefront of cancer immunotherapy development. The number of ongoing autologous and allogeneic CAR T cell clinical trials has increased exponentially, with more than 30% of studies researching solid tumor therapies. CAR T cells are genetically engineered cells with artificial CAR receptors, capable of specific targeting of antigen in MHC-independent manner. Two autologous anti-CD19 CAR T cell therapies approved in Europe and USA, tisagenlecleucel and axicabtagene ciloleucel, have been authorized for treatment of refractory or relapsed B cell acute lymphoblastic leukemia and diffuse large B cell lymphomas with potent and long-lasting responses. Unfortunately, these medicines require a long production process and are prohibitively expensive. Although allogeneic CAR T cells can cause dangerous graft-versus-host disease and have reduced persistence after transfer, there have been many developments in gene editing and biotechnology that provide solutions for these challenges. The adoption of allogeneic CAR T cells would have the benefit of decreased therapy costs, improved access and standardized production protocols allowing further cell editing and modification, improved treatment response rates. In this review article we discuss the structure of chimeric antigen receptors, manufacture of autologous CAR T cell therapies, efficacy of currently approved medications, advances and development strategies of allogeneic CAR T cell therapies for hematologic malignancies and solid tumors.

Key words: Adoptive immunotherapy, chimeric antigen receptors, axicabtagene ciloleucel, tisagenlecleucel.