Neoantigen Cancer Vaccines: Real Opportunity or Another Illusion?

Abstract

In this communication, we will analyze some important factors and immunological phenomena related to neoantigen cancer vaccines, with particular emphasis on recently published Phase I clinical trials. Several obstacles and issues are addressed that challenge the current paradigm and inquire if neoantigens, which are essentially single-use vaccine candidates, are legitimate targets to induce protective immune responses with regard to the evolving mutational landscape. We also share insights into the striking similarities between cancer and antigenically variable pathogens and suggest that any successful vaccine against either should demonstrate a similar property: efficient induction of a diverse pool of immune cells equipped to prevent immune escape. Hence, to confront antigenic variability directly, we have employed our innovative vaccine concept, Variable Epitope Libraries, composed of large combinatorial libraries of heavily mutated epitopes, as a “universal” vaccine platform. Collectively, we offer critical analyses on key issues, which ultimately reflect on the prospective clinical relevance of personalized neoantigen vaccines which is still undefined.

Personalized Neoantigen DNA Cancer Vaccines: Current Status and Future Perspectives

“…Varying vaccine formats and delivery technologies have signified that the approach is feasible and safe, and the recently published pivotal data from KEYNOTE-942 with clinical efficacy in melanoma patients corroborates the rationale and potential of NeoAg PCVs to improve the clinical outcome for cancer patients. The consensus in the field is that NeoAg PCVs constitute treatment options for cancer patients packed with both opportunities and challenges [78]. As described in this article, DNA offers a versatile platform to deliver NeoAg PCVs in clinical studies, able to elicit NeoAgspecific T cells and early evidence of clinical efficacy along with a good safety profile.…”