» Articles » PMID: 38962014

Universal CAR 2.0 to Overcome Current Limitations in CAR Therapy

Overview
Journal Front Immunol
Date 2024 Jul 4
PMID 38962014
Authors
Affiliations
Soon will be listed here.
Abstract

Chimeric antigen receptor (CAR) T cell therapy has effectively complemented the treatment of advanced relapsed and refractory hematological cancers. The remarkable achievements of CD19- and BCMA-CAR T therapies have raised high expectations within the fields of hematology and oncology. These groundbreaking successes are propelling a collective aspiration to extend the reach of CAR therapies beyond B-lineage malignancies. Advanced CAR technologies have created a momentum to surmount the limitations of conventional CAR concepts. Most importantly, innovations that enable combinatorial targeting to address target antigen heterogeneity, using versatile adapter CAR concepts in conjunction with recent transformative next-generation CAR design, offer the promise to overcome both the bottleneck associated with CAR manufacturing and patient-individualized treatment regimens. In this comprehensive review, we delineate the fundamental prerequisites, navigate through pivotal challenges, and elucidate strategic approaches, all aimed at paving the way for the future establishment of multitargeted immunotherapies using universal CAR technologies.

Citing Articles

"Attack!" Cellular Therapies to Attack Pathogens and Tumors.

Eiz-Vesper B, Bonig H Transfus Med Hemother. 2025; 52(1):1-4.

PMID: 39944410 PMC: 11813275. DOI: 10.1159/000543415.


Logic-gated and contextual control of immunotherapy for solid tumors: contrasting multi-specific T cell engagers and CAR-T cell therapies.

Nolan-Stevaux O, Smith R Front Immunol. 2024; 15:1490911.

PMID: 39606234 PMC: 11599190. DOI: 10.3389/fimmu.2024.1490911.

References
1.
Kueberuwa G, Kalaitsidou M, Cheadle E, Hawkins R, Gilham D . CD19 CAR T Cells Expressing IL-12 Eradicate Lymphoma in Fully Lymphoreplete Mice through Induction of Host Immunity. Mol Ther Oncolytics. 2018; 8:41-51. PMC: 5772011. DOI: 10.1016/j.omto.2017.12.003. View

2.
Leen A, Bollard C, Mendizabal A, Shpall E, Szabolcs P, Antin J . Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood. 2013; 121(26):5113-23. PMC: 3695359. DOI: 10.1182/blood-2013-02-486324. View

3.
Sotillo E, Barrett D, Black K, Bagashev A, Oldridge D, Wu G . Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy. Cancer Discov. 2015; 5(12):1282-95. PMC: 4670800. DOI: 10.1158/2159-8290.CD-15-1020. View

4.
Minutolo N, Sharma P, Poussin M, Shaw L, Brown D, Hollander E . Quantitative Control of Gene-Engineered T-Cell Activity through the Covalent Attachment of Targeting Ligands to a Universal Immune Receptor. J Am Chem Soc. 2020; 142(14):6554-6568. PMC: 7306176. DOI: 10.1021/jacs.9b11622. View

5.
Ukrainskaya V, Molostova O, Shelikhova L, Pershin D, Kulakovskaya E, Volkov D . Haploidentical donor-derived memory CAR T cells: first in human experience and in vitro correlative study. Blood Adv. 2022; 6(19):5582-5588. PMC: 9577623. DOI: 10.1182/bloodadvances.2021006262. View