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Mimetic Vaccines in Immuno-Oncology

A. Pashov,T. Kieber‐Emmons

Published 2019 in Cancer Immunotherapy and Biological Cancer Treatments

ABSTRACT

While the interest in cancer vaccines is renewed by some results in vaccine-based clinical trials, the premise still suffers from the incomplete concept of a successful vaccine. Future progress may come from matching preclinical data with clinical expectations while taking a step back to understand the systems perspective. A field that benefits most from this bird’s eye view is tumor immunology. For instance, the accumulation over the last three decades of clear associations of T and B cell cross-reactivity between a set of host targets of autoimmunity and microbial antigens strongly supports a pathogenic role for molecular mimicry. Mimicry on its turn invites the concept of networks of molecular interactions. The intentional and rational approach to exploit mimicry in cancer vaccine development, while littered with failure, has provided also some insight into success. Here, we visit successes and underlying rationale to lend to future development of mimetic vaccines in immune-oncology. mimotopes or idiotypes recruit B cell clones across that spectrum but their novel properties are related mostly to their capacity to elicit diversified responses from MZ and B1 cells including idiotypically connected clones. In addition, the mimotopes capture only the most salient features of the carbohydrate epitopes and induce diversified responses targeting multiple antigens (illustrated by diverse words sharing only partially the topology of the mimotope as compared to highly specific responses that match the shape of the epitope). Thus, mimetic vaccines both target polyspecific compartments of the B cell repertoire as well as they themselves function as polyspecific antigens.

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