At the bench: Engineering the next generation of cancer vaccines

Abstract

Cancer vaccines hold promise as an immunotherapeutic modality based on their potential to generate tumor antigen-specific T cell responses and long-lived antitumor responses capable of combating metastatic disease and recurrence. However, cancer vaccines have historically failed to deliver significant therapeutic benefit in the clinic, which we maintain is due in part to drug delivery challenges that have limited vaccine immunogenicity and efficacy. In this review, we examine some of the known and putative failure mechanisms of common first-generation clinical cancer vaccines, and describe how the rational design of materials engineered for vaccine delivery and immunomodulation can address these shortcomings. First, we outline vaccine design principles for augmenting cellular immunity to tumor antigens and describe how well-engineered materials can improve vaccine efficacy, highlighting recent innovations in vaccine delivery technology that are primed for integration into neoantigen vaccine development pipelines. We also discuss the importance of sequencing, timing, and kinetics in mounting effective immune responses to cancer vaccines, and highlight examples of materials that potentiate antitumor immunity through spatiotemporal control of immunomodulation. Furthermore, we describe several engineering strategies for improving outcomes of in situ cancer vaccines, which leverage local, intratumoral delivery to stimulate systemic immunity. Finally, we highlight recent innovations leveraging nanotechnology for increasing the immunogenicity of the tumor microenvironment (TME), which is critical to enhancing tumor infiltration and function of T cells elicited in response to cancer vaccines. These immunoengineering strategies and tools complement ongoing advances in cancer vaccines as they reemerge as an important component of the immunotherapeutic armamentarium.

Designing the next‐generation therapeutic vaccines to cure chronic hepatitis B: focus on antigen presentation, vaccine properties and effect measures

“…CD4 + T‐cell presentation and processing of HLA II epitopes is more promiscuous and both whole proteins and shorter fragments could be effective 21 . Furthermore, for protein‐based TV, particulation may facilitate CD8 + T‐cell induction and Th1 skewing 82 . Currently, SLP‐based vaccines for cHBV are in (pre‐) clinical development by us and others 13,72,83,84 .…”

“…21 Furthermore, for protein-based TV, particulation may facilitate CD8 + T-cell induction and Th1 skewing. 82 Currently, SLP-based vaccines for cHBV are in (pre-) clinical development by us and others. 13,72,83,84 In addition, several other proteinbased forms of antigen delivery are currently assessed in pre-clinical studies: modified cellpermeable HBV capsids are tested to deliver HBV antigens to the DCs cytoplasm to favor HLA I presentation.…”

Nucleic Acid-Based Approaches for Tumor Therapy

“…In the last decades, the potential to exploit the patients´ immune system to induce and shape anti-tumor responses has gained increasing interest [ 33 ]. The induction of tumor antigen-specific adaptive immune responses requires co-delivery of the antigen and of an immunostimulatory compound to evoke activation of a professional antigen presenting cell (APC) [ 34 ]. In this regard, DC that are considered the most potent APC population at stimulated state are in the focus of interest [ 35 ].…”

Tuberculosis–Cancer Parallels in Immune Response Regulation

“…Neoantigen discovery has the potential to benefit new CAR-T cell therapy by improving the cell targets. Additionally, in conjunction with a wide variety of proteomic and genomic techniques, cancer vaccines against tumor mutations, even specific to the mutanome of individual patients, are options being explored for cancer vaccines [ 94 , 95 , 96 , 97 , 98 , 99 ]. In particular, recent advancements with the single-cell characterization of T cells can assist in identifying specific T cell populations for therapeutic intervention [ 100 ].…”

“…In particular, recent advancements with the single-cell characterization of T cells can assist in identifying specific T cell populations for therapeutic intervention [ 100 ]. Although these methods are reliant on T cells, their relevance to tuberculosis remains low, as neoantigens are a tumor-specific phenomenon, and options for anti-cancer vaccines have been extensively reviewed elsewhere [ 96 ].…”