UCPVax, a CD4 helper peptide vaccine induces polyfunctional Th1 cells, antibody response and epitope spreading to improve antitumor immunity [scRNA-seq]

The induction of an antitumor CD4+ T helper response is essential for the efficacy of therapeutic cancer vaccines. However, few vaccines are specifically designed to target CD4+ T cells in human cancers. Here, we characterize the immune mechanisms of UCPVax, a helper peptide vaccine derived from telomerase. Ex vivo immune profiling of peripheral blood from 60 patients with advanced lung cancer reveals that UCPVax selectively activates CD4+ T cells in vivo across a broad HLA-DR restriction. The vaccine elicits a synergistic immune triad including cytokine-polyfunctional CD4+ Th1 cells, epitope spreading, and antibody response, contributing to effective tumor control. Single-cell analysis further demonstrates that UCPVax drives CD4+ T cells toward effector-memory and cytolytic differentiation. Thus, the vaccine-induced CD4+T cells trigger a broad and durable antitumor immunity. These findings highlight UCPVax as an off-the-shelf helper platform to enhance therapeutic cancer vaccine efficacy. Vaccine-induced CD4+Th1 cells were characterized using single-cell RNA sequencing. UCP-specific CD4+ T cells (IFN-γ+CD4+) were sorted from PBMC in four vaccinated patients (P023, P005 and pooled patient 020+037). PBMC collected before vaccination in one patient (P023) was used as control, PBMC collected after 12 months of treatment for P023 was also used. *************************************************************** Submitter states that missing raw files (GSM8978585, GSM8978586) are due to file loss. ***************************************************************