Genetic Engineering and CAR-T Cell Therapy inHematological Malignancies: From CD19/BCMATargeting to CRISPR-Enabled Cellular Engineering

Abstract

This research provides a comprehensive overview of genetic engineering and chimeric antigen receptor T-cell (CAR-T) therapy in the treatment of hematological malignancies. It examines the development of CAR-T cell therapies targeting clinically important antigens, particularly CD19 and B-cell maturation antigen (BCMA), with emphasis on their applications in leukemia, lymphoma, and multiple myeloma.The work discusses the molecular principles of T-cell engineering, antigen-specific targeting, gene modification, cellular manufacturing, and the role of CRISPR-based technologies in developing next-generation cellular therapies. It also explores how CRISPR-enabled genome engineering may improve CAR-T cell persistence, specificity, therapeutic activity, and resistance to tumor-mediated immune suppression.The research highlights the potential of combining genetic engineering, gene editing, immunotherapy, and precision oncology to develop more effective and personalized treatments for hematological cancers. It further considers current challenges, including treatment resistance, relapse, antigen escape, toxicity, manufacturing complexity, and the need for improved safety and long-term clinical outcomes.Overall, this work presents an interdisciplinary perspective on the evolution of CAR-T cell therapy from CD19/BCMA targeting toward advanced CRISPR-enabled cellular engineering and next-generation cancer immunotherapy.