Articles https:/ / doi.org/10.1038/s41591-022-01937-61Gritstone bio, Inc., Emeryville, CA, USA. 2Virginia Cancer Specialists, Virginia Cancer Specialists, VA, Fairfax, USA. 3The Ohio State University Medical Center, Columbus, OH, USA. 4Columbia University Medical Center, New Y ork, NY, USA. 5Peter MacCallum Cancer Centre, Melbourne, VIC, Australia. 6Mayo Clinic, Phoenix, AZ, USA. 7Mayo Clinic Cancer Center, Rochester, MN, USA. 8Memorial Sloan Kettering Cancer Center, New Y ork, NY, USA. 9The University of T exas MD Anderson Cancer Center, Houston, TX, USA. 10University of Chicago Comprehensive Cancer Center, Chicago, IL, USA. ✉e-mail: kjooss@gritstone.comCancer immunotherapies have shown promise in harnessing the immune system to target and destroy cancers, leading to clinical benefit enriched in patients with a high mutational burden 1–5. Multiple studies indicate that cytotoxic CD8 T cells tar - geting tumor neoantigens are critical to tumor control and clear - ance in response to immunotherapies targeting CTLA-4 or PD-16–10. Clinical responses to CPI therapy rely mostly on reinvigorating pre - existing tumor-specific T cell responses11, and active vaccination to expand preexisting and prime de novo tumor-specific T cells is anticipated to overcome this limitation. The limited success of cancer vaccines in the past can be attrib - uted to a number of factors, including selection of poorly immuno - genic self-antigens12, insufficiently immunogenic vaccine platforms and immunosuppressive milieus in patients with advanced cancers4. Accordingly, peptide-based neoantigen vaccine platforms have to date failed to consistently induce robust neoantigen-specific CD8 T cell responses in the majority of patients 13–15. Although more immunogenic, a homologous prime boost messenger RNA (mRNA)-based vaccination approach elicited predominantly CD4 T cell responses 16–18. Cumulatively, previous findings suggest that a successful cancer vaccine should (1) target tumor-specific neoanti - gens, (2) use highly immunogenic vaccine platform(s), (3) expand and prime T cells, (4) be combined with CPI therapy19 and (5) gen - erate long-term memory responses to ensure continuous tumor control for durable clinical benefit. Viral vector-based vaccine platforms, such as recombinant ade - novirus, are able to prime robust T cell responses20–24. Although high seroprevalence of anti-adenoviral antibodies in human populations Individualized, heterologous chimpanzee adenovirus and self-amplifying mRNA neoantigen vaccine for advanced metastatic solid tumors: phase 1 trial interim results Christine D. Palmer 1, Amy R.