Chimeric antigen receptor therapy in hematological malignancies: antigenic targets and their clinical research progress

Abstract

Chimeric antigen receptor (CAR)-based immunotherapy has achieved dramatic success in the treatment of B cell malignancies, based on the summary of current research data, and has shown good potential in early phase cancer clinical trials. Modified constructs are being optimized to recognize and destroy tumor cells more effectively. By targeting the proper B-lineage-specific antigens such as CD19 and CD20, adoptive immunotherapy has demonstrated promising clinical results and already plays a role in the treatment of several lymphoid malignancies, which highlights the importance of target selection for other CAR therapies. The high efficacy of CAR-T cells has resulted in the approval of anti-CD19-directed CAR-T cells for the treatment of B cell malignancies. In this review, we focus on the basic structure and current clinical application of CAR-T cells, detail the research progress of CAR-T for different antigenic targets in hematological malignancies, and further discuss the current barriers and proposed solutions, investigating the possible mechanisms of recurrence of CAR-T cell therapy. A summary of the paper is also given to overview as the prospects for this therapy.

The role of DNA mismatch repair in immunotherapy of human cancer

“…Therefore, applying checkpoint inhibitors is a promising strategy to combat cancer and improve survival rate through inducing genetic instability in cancer cells 119 . Therapeutic cancer vaccines such as monoclonal proteasome-targeting antibodies, agonists for co-stimulatory molecules, adoptive transfer of genetically modified T cells like chimeric antigen receptor CAR-T cells 122 , as well as agents that suppress negative regulatory pathways of T cells are all under active clinical investigation to provide longer survival time and fewer adverse reactions 123 - 125 . Despite higher requirements and more challenges putting forward, we believe more new drugs will be coming out, bringing new treatment options to patients suffering from carcinoma all over the world.…”

Targeting the Tumor Microenvironment in Neuroblastoma: Recent Advances and Future Directions

“…Recently genetic engineering of T lymphocytes to express anti-GD2 chimeric antigen receptor (CAR) has also been developed and tested in clinical trials [38][39][40]. However, despite the clinical success of CAR T cells in hematological malignancies, the efficacy of this therapy has not shown any significant benefit in solid tumors including NB due to immunosuppressive TME in neuroblastoma [30,41]. Hence, understanding the TME of NB is crucial for the generation of efficient therapeutic strategies to treat this childhood cancer.…”

CAR-NK cells in combination therapy against cancer: A potential paradigm

“…Chimeric antigen receptor (CAR)-modified immune effector cell (CAR-T/NK) therapy is a tumor adoptive therapy developed in recent years. At present, CAR-T cell therapy has been proven to be an effective tumor therapy, especially the application of CD19-targeted CAR-T cells in B cell originated leukemia and lymphoma [ 1 ]. However, extra-target toxicity, cytokine release syndrome (CRS) and graft-versus-host disease (GVHD) have limited their further clinical applications [ 2 ].…”