Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML

Frontiers in Immunology

Immunology

Andrew Kent¹  Eduardo Davila²  Lyndsey S. Crump³ 

[1] Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO, United States;Human Immunology and Immunotherapy Initiative, University of Colorado, Aurora, CO, United States;Department of Medicine, University of Colorado Comprehensive Cancer Center, Aurora, CO, United States;Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO, United States;Human Immunology and Immunotherapy Initiative, University of Colorado, Aurora, CO, United States;Department of Medicine, University of Colorado Comprehensive Cancer Center, Aurora, CO, United States;Department of Medicine, University of Colorado, Aurora, CO, United States;TrAMPoline Pharma, Inc., Aurora, CO, United States;

关键词: NK cell;    iNKT cell;    gdT cell;    adoptive cell therapy;    acute myeloid leukemia;    immune cell engineering;   

DOI  :  10.3389/fimmu.2023.1202950

 received in 2023-04-09, accepted in 2023-07-24,  发布年份 2023

来源: Frontiers

【 摘 要 】

Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immunosuppressive microenvironments, and leukemic stem cell populations elusive to immune recognition and destruction. While there are promising T cell-based therapies including chimeric antigen receptor (CAR)-T designs under development, other cytotoxic lymphocyte cell subsets have unique phenotypes and capabilities that might be of additional benefit in AML treatment. Of particular interest are the natural killer (NK) and unconventional T cells known as invariant natural killer T (iNKT) and gamma delta (γδ) T cells. NK, iNKT, and γδT cells exhibit intrinsic anti-malignant properties, potential for alloreactivity, and human leukocyte-antigen (HLA)-independent function. Here we review the biology of each of these unconventional cytotoxic lymphocyte cell types and compare and contrast their strengths and limitations as the basis for adoptive cell therapies for AML.

【 授权许可】

Unknown   
Copyright © 2023 Kent, Crump and Davila