Chimeric Antigen Receptor T-Cell Therapy: A Beacon of Hope in the Fight Against Cancer

Abstract

Despite significant advancements, relapses, and persistent malignancies are still a major challenge faced by the oncologists. Immunotherapy has shown remarkable potential in induction of sustained remission in refractory malignancies. Chimeric antigen receptor T-cell (CAR-T) therapy is a newer treatment methodology approved by the Food and Drug Administration (FDA). The chimeric pairing of an antigen receptor with the T-cell receptor (TCR) intracellular signaling domain allows cluster of designation 8 (CD8) cytotoxic T-cells to target cell surface makers independent of major histocompatibility complex (MHC) activation. Another essential feature which contributes to the broad applicability of CARs and expanding their potential targets is their ability to bind not only to proteins but also to carbohydrate and glycolipid structures. Their antigen-specific and targeted immune responses have shown promising outcomes in clinical trials particularly involving B-cell malignancies and solid tumors. High remission rates and low percentages of relapses have caused a paradigm shift in the treatment of relapsed or refractory cancers. Challenges include side effects such as cytokine release syndrome, on-target off-tumor toxicities, and replication of its success in treating solid tumors. The burden of side effects and hefty cost of treatment are major obstacles which could hinder its progress globally. Nevertheless, ongoing research would only result in a maximized therapeutic potential in addition to more patient- and cost-friendly treatment. In this review, we aim to provide the readers an overview of chimeric antigen receptor T-cell therapy, a relatively new advancement in the world of immuno-oncology and thereby also discussing its advantages, side effects and future challenges.

Emerging approaches for preventing cytokine release syndrome in CAR-T cell therapy

“…Within the cell membrane, there is an activation domain and co-stimulatory domains that amplify the CAR signal transduction pathway and increase persistence in vivo. [8][9][10] Currently, there are five FDA-approved CAR-T cell therapies for treating hematological malignancies, such as acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma (MM). 11,12 Despite their therapeutic success in treating blood-related cancers, CAR-T cells are less effective against solid tumors.…”

“…Within the cell membrane, there is an activation domain and co-stimulatory domains that amplify the CAR signal transduction pathway and increase persistence in vivo . 8–10…”

Recent progress in immunotherapy of breast cancer targeting the human epidermal growth factor receptor 2 (HER2)

“…On-target off-tumor toxicity which happens due to the effect of CAR T-cells on associated tumor antigens previously appeared on the other tissues of the body. 79,80 This immunotherapy method is worth being studied as it has shown great success compared to the infusion of monoclonal antibodies. It benefits from a non-MHC-dependent mechanism, which allows the T-cells to overcome MHC loss on the surface of tumor cells.…”

The Role of Chimeric Antigen Receptor-T Cell Therapy in the Treatment of Hematological Malignancies: Advantages, Trials, and Tribulations, and the Road Ahead

“…The success of ELIANA and ZUMA trials, resulting in FDA approval of several CAR-T cell therapies has led to progressive research related to the fourth generation and next-generation CAR-T cells, including the newest technologies, which are already under various phases of clinical trials around the world [ 45 , 46 ]. The long-term benefits will be established only after substantial positive results on a large scale.…”