From Concept to Cure: The Evolution of CAR-T Cell Therapy.

in Molecular therapy : the journal of the American Society of Gene Therapy by Kisha K Patel, Mito Tariveranmoshabad, Siddhant Kadu, Nour Shobaki, Carl June

TLDR

  • The study reviews the evolution of CAR-T cell therapy, highlighting its milestones, achievements, and challenges, with a focus on future directions and advances in the field.
  • CAR-T cell therapy has proven successful in treating hematologic malignancies, and is expanding into new areas, but faces challenges related to cost, accessibility, and toxicity.

Abstract

Chimeric antigen receptor (CAR)-T cell therapy has revolutionized cancer immunotherapy in the 21century, providing innovative solutions and life-saving therapies for previously untreatable diseases. This approach has shown remarkable success in treating various hematologic malignancies and is now expanding into clinical trials for solid tumors, such as prostate cancer and glioblastoma, as well as infectious and autoimmune diseases. CAR-T cell therapy involves harvesting a patient's T cells, genetically engineering them with viral vectors to express CARs targeting specific antigens and reinfusing the modified cells into the patient. These CAR-T cells function independently of major histocompatibility complex (MHC) antigen presentation, selectively identifying and eliminating target cells. This review highlights the key milestones in CAR-T cell evolution, from its invention to its clinical applications. It outlines the historical timeline leading to the invention of CAR-T cells, discusses the major achievements that have transformed them into a breakthrough therapy, and addresses remaining challenges, including high manufacturing costs, limited accessibility, and toxicity issues such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Additionally, the review explores future directions and advances in the field, such as developing next-generation CAR-T cells aiming to maximize efficacy, minimize toxicity, and broaden therapeutic applications.

Overview

  • The study focuses on the evolution and clinical applications of chimeric antigen receptor (CAR)-T cell therapy, highlighting its key milestones, historical timeline, and remaining challenges.
  • The methodology used involves harvesting T cells from patients, genetically engineering them with viral vectors to express CARs targeting specific antigens, and reinfusing the modified cells into the patient.
  • The primary objective of the study is to outline the historical timeline, discuss major achievements, and address challenges related to CAR-T cell therapy, as well as explore future directions and advances in the field.

Comparative Analysis & Findings

  • CAR-T cell therapy has shown remarkable success in treating various hematologic malignancies, and is now expanding into clinical trials for solid tumors, infectious, and autoimmune diseases.
  • CAR-T cells function independently of major histocompatibility complex (MHC) antigen presentation, selectively identifying and eliminating target cells.
  • Remaining challenges include high manufacturing costs, limited accessibility, and toxicity issues such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).

Implications and Future Directions

  • Developing next-generation CAR-T cells aims to maximize efficacy, minimize toxicity, and broaden therapeutic applications, addressing the current challenges and limitations of CAR-T cell therapy.
  • Advances in the field may lead to the development of more effective and accessible CAR-T cell therapies, expanding their potential applications to even more diseases.
  • Future research directions may focus on improving manufacturing processes, reducing toxicity, and enhancing the broad therapeutic potential of CAR-T cell therapy.
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