Using a mouse tumor model, Swartz et al. demonstrated that immunogenicity and antitumor responses to peptide vaccines containing a tumor-specific, Class I-restricted peptide are enhanced when the immunizing peptide also contains a Class II-restricted helper T cell epitope. The investigators then devised a clinically tractable strategy for designing antitumor peptide vaccines to ensure potent helper T cell responses by conjoining a universal Class II-restricted epitope, present from the tetanus toxoid vaccine, to Class I-restricted tumor epitopes, enhancing immunogenicity and antitumor efficacy.
Contributed by Margot O’Toole
ABSTRACT: Personalized cancer vaccines targeting neoantigens arising from somatic missense mutations are currently being evaluated for the treatment of various cancers due to their potential to elicit a multivalent, tumor-specific immune response. Several cancers express a low number of neoantigens; in these cases, ensuring the immunotherapeutic potential of each neoantigen-derived epitope (neoepitope) is crucial. In this study, we discovered that therapeutic vaccines targeting immunodominant major histocompatibility complex (MHC) I-restricted neoepitopes require a conjoined helper epitope in order to induce a cytotoxic, neoepitope-specific CD8+ T-cell response. Furthermore, we show that the universally immunogenic helper epitope P30 can fulfill this requisite helper function. Remarkably, conjoined P30 was able to unveil immune and antitumor responses to subdominant MHC I-restricted neoepitopes that were, otherwise, poorly immunogenic. Together, these data provide key insights into effective neoantigen vaccine design and demonstrate a translatable strategy using a universal helper epitope that can improve therapeutic responses to MHC I-restricted neoepitopes.
Author Info: (1) Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. Departmen
Author Info: (1) Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. Department of Pathology, Duke University Medical Center, Durham, NC, USA. Department of Surgery, Duke University Medical Center, Durham, NC, USA. (2) Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. (3) Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. Department of Pathology, Duke University Medical Center, Durham, NC, USA. Department of Surgery, Duke University Medical Center, Durham, NC, USA. (4) Department of Immunology, Duke University Medical Center, Durham, NC, USA. (5) Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, USA. (6) Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. Department of Pathology, Duke University Medical Center, Durham, NC, USA. (7) Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. (8) Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. (9) Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. (10) Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. (11) Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA. john.sampson@duke.edu. Department of Neurosurgery, Duke University Medical Center, Durham, NC, USA. john.sampson@duke.edu. Department of Pathology, Duke University Medical Center, Durham, NC, USA. john.sampson@duke.edu.
