Targeting Mutated Plus Germline Epitopes Confers Pre-clinical Efficacy of an Instantly Formulated Cancer Nano-Vaccine.

Mona O Mohsen,Said Dermime,Thomas M Kundig,Monique Vogel,Aadil El-Turabi,Gustavo Cabral-Miranda,Carsten Riether,Julius Muller,Martin F Bachmann,Silvia Salatino,Daniel E Speiser,Christiane Ruedl,Nicola Ternette,Ariane C Gomes,Alexander Knuth

doi:10.3389/fimmu.2019.01015

Abstract

Personalized cancer vaccines hold promises for future cancer therapy. Targeting neoantigens is perceived as more beneficial compared to germline, non-mutated antigens. However, it is a practical challenge to identify and vaccinate patients with neoantigens. Here we asked whether two neoantigens are sufficient, and whether the addition of germline antigens would enhance the therapeutic efficacy. We developed and used a personalized cancer nano-vaccine platform based on virus-like particles loaded with toll-like receptor ligands. We generated three sets of multi-target vaccines (MTV) to immunize against the aggressive B16F10 murine melanoma: one set based on germline epitopes (GL-MTV) identified by immunopeptidomics, another set based on mutated epitopes (Mutated-MTV) predicted by whole exome sequencing and a last set combines both germline and mutated epitopes (Mix-MTV). Our results demonstrate that both germline and mutated epitopes induced protection but the best therapeutic effect was achieved with the combination of both. Our platform is based on Cu-free click chemistry used for peptide-VLP coupling, thus enabling bedside production of a personalized cancer vaccine, ready for clinical translation.

Highlights

Melanoma is the most aggressive type of skin cancer mostly due to its high metastatic potentials [1]
Algorithm for the Generation of a Personalized Melanoma Vaccine Platform Based on VLPs
Using immunopeptidomics and whole exome sequencing we identified and predicted tumor-specific germline and mutated CTL epitopes of the B16F10 melanoma cell line

Summary

Introduction

Melanoma is the most aggressive type of skin cancer mostly due to its high metastatic potentials [1]. Scientists emphasize the need for personalized treatments, including vaccinations that target neoantigens representing the uniqueness of each patient’s tumor [2, 3]. A Platform for the Development of a Personalized Cancer Vaccine and that targeting of a single antigen allows tumors to relapse [8], it is desirable to target multiple antigens [3, 9, 10]. Targeting neoantigens by using synthetic long peptides [14], RNA-based vaccines [15], or DC-based vaccines [16] have so far only been done in patients with tumors of high mutational burden, essentially melanoma

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Results

Conclusion