In Situ Programming of CAR-T Cells: A Pressing Need in Modern Immunotherapy

• Published in: Archivum Immunologiae et Therapiae Experimentalis Vol. 71; no. 1; p. 18
• Main Authors: Śledź, Marta, Wojciechowska, Alicja, Zagożdżon, Radosław, Kaleta, Beata
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2023; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Chimeric antigen receptors; Effector cells; Immunology; Immunotherapy; Immunotherapy, Adoptive - methods; Lymphocytes; Lymphocytes T; Macrophages; Malignancy; Natural killer cells; Neurotoxicity; Pharmacology/Toxicology; Prospective Studies; Receptors, Antigen, T-Cell; Receptors, Chimeric Antigen - therapeutic use; Review; T-Lymphocytes; generation; Gene-editing tools; CAR-T cells; Adoptive cellular therapy; In-situ generation
• ISSN: 0004-069X; 1661-4917
• DOI: 10.1007/s00005-023-00683-y

Chimeric antigen receptor-T (CAR-T) cell-based therapy has become a successful option for treatment of numerous hematological malignancies, but also raises hope in a range of non-malignant diseases. However, in a traditional approach, generation of CAR-T cells is associated with the separation of patient’s lymphocytes, their in vitro modification, and expansion and infusion back into patient’s bloodstream. This classical protocol is complex, time-consuming, and expensive. Those problems could be solved by successful protocols to produce CAR-T cells, but also CAR-natural killer cells or CAR macrophages, in situ, using viral platforms or non-viral delivery systems. Moreover, it was demonstrated that in situ CAR-T induction may be associated with reduced risk of the most common toxicities associated with CAR-T therapy, such as cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and “on-target, off-tumor” toxicity. This review aims to summarize the current state-of-the-art and future perspectives for the in situ-produced CAR-T cells. Indeed, preclinical work in this area, including animal studies, raises hope for prospective translational development and validation in practical medicine of strategies for in situ generation of CAR-bearing immune effector cells.