Vikas Vikram Singh*
Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA
*Corresponding Author: Vikas Vikram Singh, Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
Received: December 03, 2021; Published: December 05, 2021
Chimeric antigen receptor T (CAR-T) cell is a novel class of immunotherapy that involves genetically manipulating immune cells derived from the patient to better recognize tumor antigen. This cell-based gene therapy has become the standard of care in some hematological malignancies including pediatric acute lymphoblastic leukemia and for certain types of Non-Hodgkin lymphomas. Three kinds of CAR-T cell therapies, Kymriah, Yescarta were approved for clinical application in 2017, and Tecartus was approved in 2020, while several others are still under the clinical trial phase. These approved therapies target CD19, a surface antigen, found on B cells. CAR-T cells have existed since the late 1980s but over the years the design has become more complex and more effective as our knowledge of how the immune system functions have expanded. There have been four generations of CAR-T cells. The first-generation CAR construct consisted of a single-chain variable fragment (ScFv) antigen-recognition domain, a transmembrane domain, and an intracellular T cell activation domain derived from the CD3 zeta chain but there was no costimulatory domain included, so these cells had limited capabilities as far as expansion and cytotoxicity were concerned. The second generation of CAR constructs addressed this limitation and added the intracellular costimulatory domain (either CD28 or 4-1BB) and are being commercially used as current CAR-T cell therapy. The third generation of CARs combined multiple costimulatory domains (e.g., CD3 ζ-CD28-41BB, CD3 ζ-CD28-OX40) to augment T cell activity. The fourth generation of CAR constructs consists of a similar co-stimulatory domain to the previous generation but adds factors such as IL12, and other costimulatory ligands which augments T-cell activation and activates innate immune cells to eliminate antigen-negative cancer cells in the targeted lesion. This generation of a CAR construct is still being investigated in preclinical studies, with the hope that they will result in better effector functionality and have improved persistence in the patient. While these constructs are improving potential efficacy for CAR-T cell therapy, there are still technical challenges involved with getting them produced and infused into patients on time. Fortunately, there has been technological developmental design to speed up the process of creating CAR-T cells and getting them to patients quickly.
Citation: Vikas Vikram Singh. “CAR-T Cell Immunotherapy: Hopes and Challenges for Cancer Treatment" 6.1 (2022): 01-02.
Copyright: © 2021 Vikas Vikram Singh. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.