Engineering Targeting Materials for Therapeutic Cancer Vaccines

Abstract

Therapeutic cancer vaccines constitute a valuable tool to educate the immune system to fight tumors and prevent cancer relapse. Nevertheless, the number of cancer vaccines in the clinic remains very limited to date, highlighting the need for further technology development. Recently, cancer vaccines have been improved by the use of materials, which can strongly enhance their intrinsic properties and biodistribution profile. Moreover, vaccine efficacy and safety can be substantially modulated through selection of the site at which they are delivered, which fosters the engineering of materials capable of targeting cancer vaccines to specific relevant sites, such as within the tumor or within lymphoid organs, to further optimize their immunotherapeutic effects. In this review, we aim to give the reader an overview of principles and current strategies to engineer therapeutic cancer vaccines, with a particular focus on the use of sitespecific targeting materials. We will first recall the goal of therapeutic cancer vaccination and the type of immune responses sought upon vaccination, before detailing key components of cancer vaccines. We will then present how materials can be engineered to enhance the vaccine's pharmacokinetic and pharmacodynamic properties. Finally, we will discuss the rationale for site-specific targeting of cancer vaccines and provide examples of current targeting technologies.

Molecular Mechanisms of Tumor Immunomodulation in the Microenvironment of Colorectal Cancer

“…In addition, these interactions can occur between different cell types, as immune cells directly interact with other immune cells, with tumor cells and with stromal cells. For example, tumor cells contain multiple surface ligands and receptors that can bind to immune cells receptors, often dampening immune mechanisms and promoting tumor cell survival [ 27 ]. Here, we detail several selected examples that illustrate tumor immunomodulatory mechanisms based on cell-cell interactions.…”

Increasing Solvent Tolerance to Improve Microbial Production of Alcohols, Terpenoids and Aromatics

“…In addition to polymerases, transcriptional regulators, etc., small RNAs (sRNAs) might also be relevant targets for tolerance engineering since they are often associated with multigene networks [ 235 ]. Indeed, two sRNAs (Zms4 and Zms6) in Z. mobilis were recently identified as important determinants for ethanol tolerance [ 236 ]. Unfortunately, the link between these sRNAs and production has not been evaluated yet, but sRNAs might potentially provide opportunities for further strain engineering.…”

From Interconnection between Genes and Microenvironment to Novel Immunotherapeutic Approaches in Upper Gastro-Intestinal Cancers—A Multidisciplinary Perspective

“…In theory, RNA-based vaccines present some potential benefits if compared to classical vaccination approaches: (i) they are pharmaceutically safer, since they cannot integrate with DNA and seem to be active in absence of serious adverse event; (ii) they can target multiple tumor-associated epitopes; (iii) they are not MHC-restricted. However, their clinical application has been limited, until now, by difficulties in obtaining stable and efficient mRNA delivery and a technical improvement is required before fully reaching the clinical scenario [ 195 , 196 ]. More integrated strategies encompass combination of vaccines with standard chemotherapy, which aims at exploiting the above-mentioned potentiality of chemotherapy to upregulate tumor immunogenicity.…”