Abstract
Cancer vaccines can generate and amplify tumor-specific T cell responses with the promise to provide long-term control of cancer. All cancer cells harbor genetic alterations encoding neoantigens that are specific to the tumor and not present in normal tissue. Similar to foreign antigens targeted by T cells in infectious disease settings, neoantigens represent the long elusive immunogens for cancer vaccination. Since the vast majority of mutations are unique to individual tumors, neoantigen vaccines require custom design for each patient. The availability of rapid and cost-effective genome sequencing, along with advanced bioinformatics tools, now allows neoantigen-target discovery and vaccine manufacturing in sufficient time for the treatment of cancer patients. Clinical trials in melanoma and glioblastoma have demonstrated the feasibility, immunogenicity, and signals of efficacy of this personalized immunotherapy approach. Key unresolved areas include identification of the most effective vaccine delivery platforms, validation and consensus of neoantigen target selection, and optimal strategies for partnering immunotherapies. Given the universal presence of mutations in cancer and the patient-tailored paradigm, personalized neoantigen vaccines have potential applicability for all cancer patients.
Highlights
Effective and long-lasting anticancer immunity relies on robust, tumor-specific T cell responses
2015); (b) frequencies of neoantigen-specific T cells were found increased in cancer patients who responded to immune checkpoint inhibition and other immunotherapies (Rizvi et al 2015, van Rooij et al 2013); and (c) direct in vivo cytotoxicity by neoantigen-specific T cells was demonstrated in various mouse models including sarcoma, melanoma, and colon cancer and in patients with treatment-resistant advanced cholangiocarcinoma or breast cancer who experienced tumor responses upon adoptive transfer of neoantigen-specific T cells (Tran et al 2014, Zacharakis et al 2018)
The clinical cancer setting requires timely identification of vaccine targets, usually from limited amounts of tumor material. This reality necessitates a compromise between, on the one hand, steps that might be on the wish list for target validation— such as conducting mass spectrometry to physically detect computationally predicted epitopes or performing in vitro immune assays to validate the antigenicity of the selected epitopes in autologous peripheral blood mononuclear cells (PBMCs)—and, on the other hand, the clinical necessity of accelerating the process of manufacturing a personalized therapeutic for a cancer patient
Summary
Annu. Rev. Cancer Biol. 2021.5:259-276. Downloaded from www.annualreviews.org Access provided by 54.226.49.157 on 11/08/21. See copyright for approved use. The Annual Review of Cancer Biology is online at cancerbio.annualreviews.org https://doi.org/10.1146/annurev-cancerbio-060820111701
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