Poster Preview
This poster summarizes strategies to enhance CAR-T cell therapy efficacy in solid tumors, including preconditioning, gene knockouts, and improved tumor infiltration to overcome limitations in current immunotherapy approaches.
College
College of Arts and Sciences
Mentor Information
Olukemia Akintewe
Description
Chimeric Antigen Receptor T-cell (CAR-T) therapy is a powerful form of immunotherapy that has shown success in treating blood cancers. CAR-T cells often face challenges that limit their overall effectiveness; hence, researchers are focusing on strategies that improve how well CAR-T cells survive, grow, and target cancer cells. This review was conducted to analyze how CAR-T cells are constructed, highlight the major barriers that limit CAR-T’s efficacy, and determine how to improve it through preconditioning, gene knockouts, and enhanced infiltration. Literature was found through the PubMed, Scopus, and Web of Science databases. The following key search terms and synonyms were incorporated into the search algorithm: “preconditioning,” “immunosuppression,” “genetic knockout,” and “tumor infiltration.” All articles written within the last five years were screened. A total of 44 articles met the inclusion criteria and were used. Analysis of the studies found three main strategies that improve CAR-T cell efficacy. Preconditioning approaches, including lymphodepletion and cytokine modulation, enhanced CAR-T expansion, persistence, and antitumor activity by reducing the immunosuppressive elements of the tumor microenvironment. Gene knockout strategies, such as disruptions of PD-1 or TGF-β signaling, improved CAR-T durability, resistance to inhibitory signals, and cytotoxic functions. Enhanced infiltration methods, like chemokine receptor engineering and matrix-modifying approaches, increased CAR-T penetration and localization into tumor sites. This review highlights how strategic preconditioning, targeted gene knockouts, and improved tumor infiltration can address the key limitations of CAR-T therapy, emphasizing the importance of continued research for safer and more effective cancer immunotherapies.
Strategies to Improve CAR-T Efficacy: Preconditioning, Gene Knockouts, and Enhancing Infiltration
Chimeric Antigen Receptor T-cell (CAR-T) therapy is a powerful form of immunotherapy that has shown success in treating blood cancers. CAR-T cells often face challenges that limit their overall effectiveness; hence, researchers are focusing on strategies that improve how well CAR-T cells survive, grow, and target cancer cells. This review was conducted to analyze how CAR-T cells are constructed, highlight the major barriers that limit CAR-T’s efficacy, and determine how to improve it through preconditioning, gene knockouts, and enhanced infiltration. Literature was found through the PubMed, Scopus, and Web of Science databases. The following key search terms and synonyms were incorporated into the search algorithm: “preconditioning,” “immunosuppression,” “genetic knockout,” and “tumor infiltration.” All articles written within the last five years were screened. A total of 44 articles met the inclusion criteria and were used. Analysis of the studies found three main strategies that improve CAR-T cell efficacy. Preconditioning approaches, including lymphodepletion and cytokine modulation, enhanced CAR-T expansion, persistence, and antitumor activity by reducing the immunosuppressive elements of the tumor microenvironment. Gene knockout strategies, such as disruptions of PD-1 or TGF-β signaling, improved CAR-T durability, resistance to inhibitory signals, and cytotoxic functions. Enhanced infiltration methods, like chemokine receptor engineering and matrix-modifying approaches, increased CAR-T penetration and localization into tumor sites. This review highlights how strategic preconditioning, targeted gene knockouts, and improved tumor infiltration can address the key limitations of CAR-T therapy, emphasizing the importance of continued research for safer and more effective cancer immunotherapies.
