Engineered CD4 TCR T cells with conserved high-affinity TCRs targeting NY-ESO-1 for advanced cellular therapies in cancer.

ABSTRACT: While cancer immunotherapy has primarily focused on CD8 T cells, CD4 T cells are increasingly recognized for their role in antitumor immunity. The HLA-DRB3*02:02 allele is found in 50% of Caucasians. In this study, we screened HLA-DRB3*02:02 patients with melanoma for tumor-specific CD4 T cells and identified robust New York esophageal squamous cell carcinoma 1 (NY-ESO-1)_123-137/HLA-DRB3*02:02 CD4 T cell activity in both peripheral blood and tumor tissue. By analyzing NY-ESO-1_123-137/HLA-DRB3*02:02-restricted CD4 T cell clones, we uncovered an unexpectedly high cytotoxicity, strong T helper 1 polarization, and recurrent αβ T cell receptor (TCRαβ) usage across patients and anatomical sites. These responses were also present in other NY-ESO-1

SUBMITTER: Saillard M 

PROVIDER: S-EPMC12204177 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature