Lahuerte et al. developed and tested UCPVax – an off-the-shelf CD4+ T cell-targeted vaccine containing two universal cancer peptides (UCPs; pan-HLA-DR-binding peptides) derived from human telomerase reverse transcriptase (hTERT; a widely expressed TAA). Following ex vivo immune profiling of peripheral blood from patients with advanced NSCLC who were treated with UCPVax in a phase 1/2 clinical trial, the researchers found that UCPVax stimulated CD4+ T cells across a broad range of HLA-DR alleles, driving CD4+ T cells towards polyfunctional, cytolytic, and effector memory states, and supporting epitope spreading, antibody responses, and antitumor immunity.
Contributed by Lauren Hitchings
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.
Author Info: (1) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France. (2) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France. (3) Un
Author Info: (1) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France. (2) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France. (3) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France. (4) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France. (5) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne and Lausanne University Hospital, Lausanne, Switzerland. (6) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne and Lausanne University Hospital, Lausanne, Switzerland. (7) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France. (8) Computational Oncology Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. (9) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France. (10) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France. (11) Clinical Investigational Center, CIC-1431, Centre Hospitalier Universitaire de Besanon, Besanon, France. (12) Methodology and Quality of Life in Oncology Unit, University Hospital of Besanon, Besanon, France. (13) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France; Methodology and Quality of Life in Oncology Unit, University Hospital of Besanon, Besanon, France. (14) Department of Medical Oncology, Centre Georges-Franois Leclerc, Dijon, France. (15) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France. (16) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne and Lausanne University Hospital, Lausanne, Switzerland; Department of Oncology UNIL CHUV, University Hospital of Lausanne, Lausanne, Switzerland. (17) Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne and Lausanne University Hospital, Lausanne, Switzerland; Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland; Geneva Center for Inflammation Research, Geneva, Switzerland. (18) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France; Clinical Investigational Center, CIC-1431, Centre Hospitalier Universitaire de Besanon, Besanon, France; Department of Medical Oncology, University Hospital of Besanon, 25000 Besanon, France. (19) Universit Marie et Louis Pasteur, EFS, INSERM, UMR RIGHT, 25000 Besanon, France; Department of Medical Oncology, University Hospital of Besanon, 25000 Besanon, France. Electronic address: olivier.adotevi@univ-fcomte.fr.
