Language
English
Publication Date
11-2-2022
Journal
Cancer Immunology Research
DOI
10.1158/2326-6066.CIR-22-0115
PMID
36122411
PMCID
PMC9633434
PubMedCentral® Posted Date
5-2-2023
PubMedCentral® Full Text Version
Author MSS
Abstract
T-cell immunotherapy has demonstrated remarkable clinical outcomes in certain hematologic malignancies. However, efficacy in solid tumors has been suboptimal, partially due to the hostile tumor microenvironment composed of immune-inhibitory molecules. One such suppressive agent abundantly expressed in solid tumors is Fas ligand (FasL), which can trigger apoptosis of Fas-expressing effector cells such as T cells and natural killer (NK) cells. To alleviate this FasL-induced suppression of tumor-specific immune cells in solid tumors, we describe here the development of a Fas decoy that is secreted by engineered cells upon activation and sequesters the ligand, preventing it from engaging with Fas on the surface of effector cells. We further improved the immune-stimulatory effects of this approach by creating a Fas decoy and IL15 cytokine fusion protein, which enhanced the persistence and antitumor activity of decoy-engineered as well as bystander chimeric-antigen receptor (CAR) T cells in xenograft models of pancreatic cancer. Our data indicate that secreted Fas decoys can augment the efficacy of both adoptively transferred and endogenous tumor-specific effector cells in FasL-expressing solid tumors.
Keywords
Humans, Fas Ligand Protein, T-Lymphocytes, Neoplasms, Tumor Microenvironment, Killer Cells, Natural, Cancer immunotherapy, Adoptive T cell therapy, Chimeric Antigen Receptor, CAR T cells
Published Open-Access
yes
Recommended Citation
Bajgain, Pradip; Torres Chavez, Alejandro G; Balasubramanian, Kishore; et al., "Secreted Fas Decoys Enhance the Antitumor Activity of Engineered and Bystander T Cells in Fas Ligand-Expressing Solid Tumors" (2022). Faculty and Staff Publications. 4609.
https://digitalcommons.library.tmc.edu/baylor_docs/4609