The Changing Landscape of Therapeutic Cancer Vaccines—Novel Platforms and Neoantigen Identification

Abstract

Therapeutic cancer vaccines, an exciting development in cancer immunotherapy, share the goal of creating and amplifying tumor-specific T-cell responses, but significant obstacles still remain to their success. Here, we briefly outline the principles underlying cancer vaccine therapy with a focus on novel vaccine platforms and antigens, underscoring the renewed optimism. Numerous strategies have been investigated to overcome immunosuppressive mechanisms of the tumor microenvironment (TME) and counteract tumor escape, including improving antigen selection, refining delivery platforms, and use of combination therapies. Several new cancer vaccine platforms and antigen targets are under development. In an effort to amplify tumorspecific T-cell responses, a heterologous prime-boost antigen delivery strategy is increasingly used for virus-based vaccines.Viruses have also been engineered to express targeted antigens and immunomodulatory molecules simultaneously, to favorably modify the TME. Nanoparticle systems have shown promise as delivery vectors for cancer vaccines in preclinical research. T-win is another platform targeting both tumor cells and the TME, using peptide-based vaccines that engage and activate T cells to target immunoregulatory molecules expressed on immunosuppressive and malignant cells. With the availability of next-generation sequencing, algorithms for neoantigen selection are emerging, and several bioinformatic platforms are available to select therapeutically relevant neoantigen targets for developing personalized therapies. However, more research is needed before the use of neoepitope prediction and personalized immunotherapy becomes commonplace. Taken together, the field of therapeutic cancer vaccines is fast evolving, with the promise of potential synergy with existing immunotherapies for long-term cancer treatment.

Emerging Next-Generation Target for Cancer Immunotherapy Research: The Orphan Nuclear Receptor NR2F6

“…Fortunately, in this context, tumors are often genetically unstable and thus show a high mutational burden that generates unique tumor-specific neoantigens (nAg), which are non-self-peptides without pre-existing central tolerance [ 14 ]. nAg vaccination approaches seem to be superior due to the reduced risk of inducing autoimmunity and due to a lower activation threshold of nAg-specific T lymphocytes, since there is no need to break immune tolerance of self-antigens for an efficient anti-tumor response (reviewed in [ 15 ]). However, because neoantigens frequently differ between patients, personalized vaccination protocols are needed, making them more expensive and less feasible for their wide use in clinical practice.…”

Monitoring T Cells Responses Mounted by Therapeutic Cancer Vaccines

“…Whilst RNA is similar to DNA, it is less stable and requires a cold-chain for transportation. However, both DNA and RNA have limited delivery efficacy (Jou et al, 2021). Peptide vaccines are peptides of 9-25 amino acid in length designed based on the prediction of specific regions of an antigen that can bind to MHC-I and II molecules.…”

“…As cancer vaccines targeting tumor associated antigen or protein often induce central tolerance where clinical benefit may be limited (Jou et al, 2021), packaging the antigen of interest into oncolytic viruses is known to improve its immunogenicity and efficacy. Genetically modified oncolytic viruses can replicate selectively in tumor cells and promote tumor cell lysis, at the…”

Prophylactic Cancer Vaccines Engineered to Elicit Specific Adaptive Immune Response

“…The goal of preventative cancer vaccines is not to treat, but to prevent the development of a tumor. Cancer vaccines are often defined as therapeutic vaccines, which are different from prophylactic vaccines in that they elicit an immune response to an existing tumor and to residual cancer cells following other treatments (6). Therapeutic vaccines against cancer elicit immune responses following the onset of disease.…”