Mimetic Vaccines in Immuno-Oncology

Abstract

While the interest in cancer vaccines is renewed by some results in vaccinebased 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.Keywords: vaccine, anti-idiotype, peptide, tumor associated carbohydrate antigens, carbohydrate mimetic peptide Cancer Immunotherapy and Biological Cancer Treatments 2 requires alternative immunotherapeutic strategies. One such strategy is to develop polyclonal humoral immune responses by active immunotherapy. Itself, this concept can have multiple approaches and an orchestra of potential mechanisms that encompass a dynamic systems immunology perspective (Figure 1). On the one hand the effect can be pursued by formulating a platform with multiple epitopes of target antigens [19]. On the other-making use of polyspecific (pan-antigen) mimetics to target simultaneously multiple antigens on cancer cells [17, 18]. A polyclonal antibody approach would target more than two antigens on a single tumor cell, which is expected to have even higher potential. This latter idea is a part of the conceptual evolution in immune-oncology harnessing polyclonal responses to cancer cells. Setting the stage: systems conceptsSystems immunology is now in focus to understand the immune system [20], especially in the context of vaccinology [21]. This perspective is ushering in a new era in vaccine development [22]. For the future, it is argued that successful approaches will depend on the elucidation of the entire network of immune signaling pathways that regulate immune responses with an eye toward integrating advances in computational and systems biology, genomics, immune monitoring, bioinformatics and machine learning [22,23].Systems immunology also teaches us that one antigen can substitute for another having the potential to regulate tolerance [24][25][26][27][28]. However, it is unclear why an immune system that is tolerant of its own self-antigens would respond to a self-antigen mimic in a vaccine. Antibodies referred to as anti-idiotypic are produced during