Abstract
Cancer neoantigens derived from random somatic mutations in tumor tissue represent an attractive type of targets for the cancer immunotherapies including cancer vaccine. Vaccination against the tumor-specific neoantigens minimizes the potential induction of central and peripheral tolerance as well as the risk of autoimmunity. Neoantigen-based cancer vaccines have recently showed marked therapeutic potential in both preclinical and early-phase clinical studies. However, significant challenges remain in the effective and faithful identification of immunogenic neoepitopes and the efficient and safe delivery of the subunit vaccine components for eliciting potent and robust anticancer T cell responses. In this mini review, we provide a brief overview of the recent advances in the development of neoantigen-based cancer vaccines focusing on various vaccine delivery strategies for targeting and modulating antigen-presenting cells. We discuss current delivery approaches, including direct injection, ex vivo-pulsed dendritic cell vaccination, and biomaterial-assisted vaccination for enhancing the efficiency of neoantigen vaccines and present a perspective on future directions.
Highlights
Vaccines activating the immune system for prevention and treatment of infections and other diseases have made major impact in human healthcare
We summarize and discuss the recent prog ress in addressing these issues for the development of neoantigenbased cancer vaccines with an emphasis on various delivery strategies
In order to maximize the capture of antigens by antigen-presenting cells (APCs), unformulated In vitro transcribed (IVT) mRNA can be administered directly into lymph nodes (LNs) through ultrasound-guided percutaneous injection [noted as intranodal (i.n.) injection], a clinically applicable administration route for the direct access to inner organs or tissues through needlepuncture of the skin [47]. Sahin and his group demonstrated an elegant example of immunizing advanced melanoma patients in a clinical study using vaccines based on synthetic mRNAs encoding poly-neoepitopes through i.n. injection (Table 1) [16]
Summary
Vaccines activating the immune system for prevention and treatment of infections and other diseases have made major impact in human healthcare. Three independent clinical studies provided solid evidence that neoantigen-based cancer vaccines could be deve loped to elicit potent neoantigen-specific T cell responses against late stage melanoma with remarkable safety and efficacy [15,16,17].
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