# UCPVax, a CD4 helper peptide vaccine, induces polyfunctional Th1 cells, antibody response, and epitope spreading to improve antitumor immunity

## TL;DR

UCPVax is a cancer vaccine that activates CD4+ T cells, boosts immune responses, and improves tumor control through multiple mechanisms.

## Contribution

UCPVax is a novel CD4 helper peptide vaccine that elicits polyfunctional Th1 cells, epitope spreading, and antibody responses to enhance antitumor immunity.

## Key findings

- UCPVax activates CD4+ T cells across a broad HLA-DR restriction in lung cancer patients.
- The vaccine induces polyfunctional Th1 cells, epitope spreading, and antibody responses.
- UCPVax promotes CD4+ T cell differentiation into effector memory and cytolytic cells.

## Abstract

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, vaccine-induced CD4+ T cells trigger broad and durable antitumor immunity. These findings highlight UCPVax as an off-the-shelf helper platform to enhance therapeutic cancer vaccine efficacy. This study was registered at ClinicalTrials.gov: NCT02818426.

•UCPVax vaccination stimulates CD4+ T cells across a broad MHC class II context•UCPVax drives CD4+ T cells toward polyfunctional and cytolytic Th1 polarization•Induction of strong epitope spreading and antibody response after UCPVax vaccination•These UCPVax-induced immune responses contribute to tumor control

UCPVax vaccination stimulates CD4+ T cells across a broad MHC class II context

UCPVax drives CD4+ T cells toward polyfunctional and cytolytic Th1 polarization

Induction of strong epitope spreading and antibody response after UCPVax vaccination

These UCPVax-induced immune responses contribute to tumor control

CD4+ T cell stimulation is critical for cancer vaccine efficacy. Laheurte et al. describe the properties of UCPVax, a CD4 helper cancer vaccine derived from telomerase that triggers polyfunctional Th1 cells with cytolytic properties, generates robust antibody responses, and promotes strong epitope spreading—factors that contribute to optimal tumor control.