key: cord-0763103-3u0t1ok7 authors: Antonarelli, G.; Corti, C.; Tarantino, P.; Ascione, L.; Cortes, J.; Romero, P.; Mittendorf, E.A.; Disis, M.L.; Curigliano, G. title: Therapeutic Cancer Vaccines Revamping: Technology Advancements and Pitfalls date: 2021-09-06 journal: Ann Oncol DOI: 10.1016/j.annonc.2021.08.2153 sha: 5e6187d8eb7eb0570a8223d3f412df3d990b9115 doc_id: 763103 cord_uid: 3u0t1ok7 Cancer vaccines (CVs) represent a long-sought therapeutic and prophylactic immunotherapy strategy to obtain antigen-specific T-cell responses, and potentially achieve long-term clinical benefit. However, historically, most CV clinical trials have resulted in disappointing outcomes, despite promising signs of immunogenicity across most formulations. In the past decade, technologic advances regarding vaccine delivery platforms, tools for immunogenomic profiling and antigen/epitope selection have occurred. Consequently, the ability of CVs to induce tumor-specific and, in some cases, remarkable clinical responses have been observed in early-phase clinical trials. It is notable that the record-breaking speed of vaccine development in response to the coronavirus disease (COVID-19) pandemic mainly relied on manufacturing infrastructures and technological platforms already developed for CVs. In turn, research, clinical data, and infrastructures put in place for the SARS-CoV2 pandemic can further speed CV development processes. This review outlines the main technological advancements as well as major issues to tackle in the development of CVs. Possible applications for unmet clinical needs will be described, putting into perspective the future of cancer vaccinology. Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes. Two 960 in one: improving synthetic long peptide vaccines by combining antigen and adjuvant in 961 one molecule Vaccination with 964 synthetic long peptide formulated with CpG in an oil-in-water emulsion induces robust 965 E7-specific CD8 T cell responses and TC-1 tumor eradication Optimizing safety surveillance for COVID-19 vaccines Catalogue Of Somatic Mutations In Cancer Meta-1015 analysis of tumor-and T cell-intrinsic mechanisms of sensitization to checkpoint 1016 inhibition Small molecules, big impact: 20 years of 1018 targeted therapy in oncology ESR1 mutations-a 1020 mechanism for acquired endocrine resistance in breast cancer The Immunogenic Potential of Recurrent Circulating tumour DNA in patients with advanced melanoma treated with dabrafenib or 1033 dabrafenib plus trametinib: a clinical validation study. The Lancet Oncology Longitudinal 1036 tracking of 97 esophageal adenocarcinomas using liquid biopsy sampling. Annals of 1037 Oncology Therapeutic cancer 1039 vaccines T Cell Epitope Predictions Their mechanism of action is multimodal, as the injection of OVs in 1092 primary/accessible tumors induces immunogenic cell death (ICD) of tumor cells, promoting 1093 the build-up of an inflamed TME (71). In fact, OVs support Natural Killer (NK)-cell and T-cell 1094 immune responses, ultimately improving the lysis of OV-infected cancer cells. Moreover, the 1095 activation of antiviral innate immunity