| Reference |
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| Reference Type | Literature | IEDB_Reference:1042251 |
| Title | mRNA vaccine-induced neoantigen-specific T cell immunity in patients with gastrointestinal cancer. | |
| Authors | Gal Cafri; Jared J Gartner; Tal Zaks; Kristen Hopson; Noam Levin; Biman C Paria; Maria R Parkhurst; Rami Yossef; Frank J Lowery; Mohammad S Jafferji; Todd D Prickett; Stephanie L Goff; Christine T McGowan; Samantha Seitter; Mackenzie L Shindorf; Anup Parikh; Praveen D Chatani; Paul F Robbins; Steven A Rosenberg | |
| Affiliations | Surgery Branch, National Cancer Institute (NCI), NIH, Bethesda, Maryland, USA; Sheba Medical Center, Ramat Gan, Israel; Moderna Inc., Cambridge, Massachusetts, USA. | |
| Journal | J Clin Invest | |
| Year | 2020 | |
| Abstract | BACKGROUNDTherapeutic vaccinations against cancer have mainly targeted differentiation antigens, cancer-testis antigens, and overexpressed antigens and have thus far resulted in little clinical benefit. Studies conducted by multiple groups have demonstrated that T cells recognizing neoantigens are present in most cancers and offer a specific and highly immunogenic target for personalized vaccination.METHODSWe recently developed a process using tumor-infiltrating lymphocytes to identify the specific immunogenic mutations expressed in patients' tumors. Here, validated, defined neoantigens, predicted neoepitopes, and mutations of driver genes were concatenated into a single mRNA construct to vaccinate patients with metastatic gastrointestinal cancer.RESULTSThe vaccine was safe and elicited mutation-specific T cell responses against predicted neoepitopes not detected before vaccination. Furthermore, we were able to isolate and verify T cell receptors targeting KRASG12D mutation. We observed no objective clinical responses in the 4 patients treated in this trial.CONCLUSIONThis vaccine was safe, and potential future combination of such vaccines with checkpoint inhibitors or adoptive T cell therapy should be evaluated for possible clinical benefit in patients with common epithelial cancers.TRIAL REGISTRATIONPhase I/II protocol (NCT03480152) was approved by the IRB committee of the NIH and the FDA.FUNDINGCenter for Clinical Research, NCI, NIH. | |
| Curation Last Updated | 2025-08-13 08:29:57 | |