Targeted expansion of cytotoxic T cells using IL-12 and CD137L supplementation enhances antitumor efficacy

Authors

Marta Sanz, Departments of Microbiology Immunology and Tropical Medicine, George Washington University, Washington, DC 20037, USA.
Brendan T. Mann, Departments of Microbiology Immunology and Tropical Medicine, George Washington University, Washington, DC 20037, USA.
Elyse K. McMahon, Departments of Microbiology Immunology and Tropical Medicine, George Washington University, Washington, DC 20037, USA.
Alberto Bosque, Departments of Microbiology Immunology and Tropical Medicine, George Washington University, Washington, DC 20037, USA.
Samuel Simmens, Biostatistics, George Washington University, Washington, DC 20037, USA.
Natalia Soriano-Sarabia, Departments of Microbiology Immunology and Tropical Medicine, George Washington University, Washington, DC 20037, USA.

Document Type

Journal Article

Publication Date

6-18-2025

Journal

Molecular therapy. Oncology

Volume

33

Issue

2

DOI

10.1016/j.omton.2025.200996

Keywords

CD137L; MT: Regular Issue; Vd2 cells; alendronate; cancer; cell therapy; cytotoxicity; expansion; gamma delta T cells; oncology

Abstract

The increasing success of allogenic Vδ2 T cell immunotherapy for the treatment of cancer has been demonstrated in recent studies. Vδ2 T cells recognize phosphoantigens, intermediates of the mevalonate pathway, through butyrophilin molecules, and they are not major histocompatibility complex (MHC) restricted. Allogeneic transfer of in vitro expanded Vδ2 T cells has shown more promising results than autologous strategies, although the clinical benefit remains limited. One of the issues leading to less-than-optimal responses relates to the polyclonal expansion of Vδ2 T cell subsets with variable cytotoxic capacity. Previous work developed protocols to expand Vδ2 T cells, although to our knowledge, ours is the first comprehensive study that has produced a simple, antigen-presenting feeder-free culture that produced an average expansion of 3,000-fold and more than 95% pure Vδ2 T cells avoiding additional isolation steps. Here, we show the in vitro expansion of cytotoxic Vδ2 T cells expressing CD16 and NKG2A enriched in granzyme B that displayed enhanced antitumor activity of up to 40% against leukemia and ovarian, breast, and lung cancer cells. Our work warrants clinical testing to evaluate the therapeutic potential of these highly cytotoxic cells, paving the way for improved efficacy of personalized cell-based immunotherapies.

APA Citation

Sanz, Marta; Mann, Brendan T.; McMahon, Elyse K.; Bosque, Alberto; Simmens, Samuel; and Soriano-Sarabia, Natalia, "Targeted expansion of cytotoxic T cells using IL-12 and CD137L supplementation enhances antitumor efficacy" (2025). GW Authored Works. Paper 7404.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/7404

Department

Biostatistics and Bioinformatics