Next-Generation Chimeric Antigen Receptors for T- and Natural Killer-Cell Therapies Against Cancer

Authors

Ye Li
Katayoun Rezvani
Hind Rafei

Publication Date

11-1-2023

Journal

Immunological Reviews

Abstract

Adoptive cellular therapy using chimeric antigen receptor (CAR) T cells has led to a paradigm shift in the treatment of various hematologic malignancies. However, the broad application of this approach for myeloid malignancies and solid cancers has been limited by the paucity and heterogeneity of target antigen expression, and lack of bona fide tumor-specific antigens that can be targeted without cross-reactivity against normal tissues. This may lead to unwanted on-target off-tumor toxicities that could undermine the desired antitumor effect. Recent advances in synthetic biology and genetic engineering have enabled reprogramming of immune effector cells to enhance their selectivity toward tumors, thus mitigating on-target off-tumor adverse effects. In this review, we outline the current strategies being explored to improve CAR selectivity toward tumor cells with a focus on natural killer (NK) cells, and the progress made in translating these strategies to the clinic.

Keywords

Humans, Receptors, Chimeric Antigen, T-Lymphocytes, Receptors, Antigen, T-Cell, Neoplasms, Immunotherapy, Adoptive, Killer Cells, Natural, Antigens, Neoplasm

DOI

10.1111/imr.13255

PMID

37548050

PMCID

PMC10841677

PubMedCentral® Posted Date

11-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes