UCPVax, a CD4 helper peptide vaccine induces polyfunctional Th1 cells, antibody response and epitope spreading to improve antitumor immunity [TCR-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. TCRβ sequencing was perfomed on vaccine-induced CD4+T cells from four patients (P023, P005, P20, P37). Negative fraction (Bulk CD4) was collected in these patients as control. Bulk CD4 collected before vaccination in one patient (P023) was also used as reference.