{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,12]],"date-time":"2026-11-12T08:25:28Z","timestamp":1794471928605,"version":"4.9.1"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Elicio Therapeutics"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Cellular immunity, mediated by tumor antigen-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, has a critical role in the success of cancer immunotherapy by targeting intracellular driver and passenger tumor mutations. We present the final results of the phase 1 AMPLIFY-201 trial, in which patients who completed standard locoregional treatment, with minimal residual mKRAS disease (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200925, 20 pancreatic cancer and 5 colorectal cancer), received monotherapy vaccination with lymph node-targeting ELI-002 2P, including mutant KRAS (mKRAS) amphiphile-peptide antigens (G12D, G12R) and amphiphile-adjuvant CpG-7909. At a median follow-up of 19.7 months, efficacy correlated with mKRAS-specific T cell responses above or below a threshold 9.17-fold increase over baseline, with median radiographic relapse-free survival not reached, versus 3.02 months (hazard ratio (HR)\u2009=\u20090.12,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0002) and median overall survival not reached versus 15.98 months (HR\u2009=\u20090.23,\n                    <jats:italic>P<\/jats:italic>\n                    \u2009=\u20090.0099). Seventy-one percent of evaluable patients induced both CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    subsets, with sustained immunogenicity. Following ELI-002 2P treatment, antigen spreading was observed in 67% of patients, with increased T cells reactive to personalized, tumor antigens absent from the ELI-002 2P vaccine. Therefore, lymph node-targeting amphiphile vaccination induces persistent T cell responses targeting oncogenic driver KRAS mutations, alongside personalized, tumor antigen-specific T cells, which may correlate to clinical outcomes in pancreatic and colorectal cancer. ClinicalTrials.gov registration:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT04853017?term=NCT04853017&amp;rank=1\" ext-link-type=\"uri\">NCT04853017<\/jats:ext-link>\n                    .\n                  <\/jats:p>","DOI":"10.1038\/s41591-025-03876-4","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T15:03:15Z","timestamp":1754924595000},"page":"3648-3653","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["Lymph node-targeted, mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer: phase 1 AMPLIFY-201 trial final results"],"prefix":"10.1038","volume":"31","author":[{"given":"Zev A.","family":"Wainberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colin D.","family":"Weekes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3137-2053","authenticated-orcid":false,"given":"Muhammad","family":"Furqan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5169-7085","authenticated-orcid":false,"given":"Pashtoon M.","family":"Kasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2290-1884","authenticated-orcid":false,"given":"Craig E.","family":"Devoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis D.","family":"Leal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James R.","family":"Perry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thian","family":"Kheoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa K.","family":"McNeil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Welkowsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"DeMuth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8600-9548","authenticated-orcid":false,"given":"Christopher M.","family":"Haqq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9281-480X","authenticated-orcid":false,"given":"Shubham","family":"Pant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8076-9199","authenticated-orcid":false,"given":"Eileen M.","family":"O\u2019Reilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"3876_CR1","doi-asserted-by":"publisher","first-page":"4973","DOI":"10.1158\/1078-0432.CCR-19-0197","volume":"25","author":"VP Groot","year":"2019","unstructured":"Groot, V. 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C.D.W. reports research funding from Elicio Therapeutics, Novartis, Actuate Therapeutics, Merck, AstraZeneca, Deciphera Pharmaceuticals, Genentech\/Roche and Mirati, and advisory board relationship with Ipsen, Celgene, Merrimack, Actuate Therapeutics and Genentech. M.F. received research funding (institutional) from AbbVie\/Stemcentrx, AstraZeneca\/MedImmune, BeiGene, Biothera, Bristol-Myers Squibb\/Celgene, Eli Lilly, Merck, Mirati Therapeutics, Novartis, Pfizer, Roche, Genmab, Elicio Therapeutics, Mirati, Amgen, Replimmune, Checkmate Pharmaceuticals, Gilead, GSK, Immunocore, Seagen, Tesaro and AbbVie, and also served on advisory boards for AbbVie, BeiGene, Jazz Pharma, Mirati, AstraZeneca\/MedImmune, Novartis and Omega Therapeutics. P.M.K. reports consultancy\/advisory board relationship with Elicio (Scientific Advisory Board Member\/Stock Ownership); is a founder of Precision BioSensors; has consultancy\/advisory board relationships with Agenus, Astellas, AstraZeneca, Beixon, Elicio Therapeutics, Guardant Health, Illumina, Natera, Foundation Medicine, Daiichi Sankyo, Tempus, Bayer, MSD Oncology\/Merck, Neogenomics, Delcath Systems, QED, Taiho Oncology (self\/institution), Exact Sciences, Eisai, BostonGene, Neogenomics, Saga Diagnostics, Regeneron, Servier, Seagen, Lilly, Xilio Therapeutics and Ipsen (to institution); and receives research funding or trial support from Merck, Novartis and Agenus Bio (all to institution). C.E.D. reports receiving honoraria from Vivacitas, a consultancy\/advisory board relationship with Pfizer and research funding (to institution) from Elicio Therapeutics. A.D.L. reports receiving honoraria from the MedPro Specialty Advisory Board and holds institutional contracts with Elicio Therapeutics, Bristol-Myers Squibb, Exelixis, FameWave, Antengene, Arrys Therapeutics, Hutchison Medipharma, Corcept Therapeutics, Conjupro Biotherapeutics, Takeda and AbbVie for clinical trials in which she serves as the local Principal Investigator. She also serves as the co-chair of the Pancreatic Cancer\/Neuroendocrine Committee on Elsevier ClinicalPath Oncology. V.C. has held consulting or advisory roles with Ipsen, Gritstone Oncology, Westwood Bioscience, Perthera, and Apeiron Biologics. He has served on the speakers\u2019 bureau for Ipsen and Celgene, and has received research funding from Elicio Therapeutics, Roche and Merck. J.R.P., E.W., L.K.M., P.C.D., T.K. and C.M.H. are employees of Elicio Therapeutics and, as such, receive salary and benefits, including ownership of stock and stock options from the company. L.K.M., P.C.D. and C.M.H. have amphiphile vaccine patents pending to Elicio Therapeutics. S.P. reports clinical research funding (to institution) from Amal Therapeutics, Arqule, Bristol-Myers Squibb, Eli Lilly, Elicio Therapeutics, Holy Stone Healthcare, Immuneering, ImmunoMET, Ipsen, Mirati Therapeutics, Novartis, Purple Biotech, Rgenix, Sanofi-Aventis, Xencor, Astellas, Framewave, 4D Pharma, Boehringer Ingelheim, NGM Biopharmaceuticals, Janssen, Arcus Biosciences, BioNTech, Zymeworks and Pfizer. Other than financial relationships, consultant\/advisory fees were received from Alligator Bioscience, Askgene Pharma, AstraZeneca, BPGBio, Zymeworks, Ipsen, Nihon Medi-Physics, Novartis, Janssen, Jazz Pharmaceuticals, US WorldMeds and Boehringer Ingelheim. E.M.O\u2019R. reports receiving research funding (to institution) from Genentech\/Roche, BioNTech, Bristol-Myers Squibb, AstraZeneca, Arcus, Elicio Therapeutics, Helsinn Healthcare, Parker Institute, NIH\/NCI, Puma Biotechnology, Digestive Care, Break Through Cancer, Agenus, Amgen, Revolution Medicines, QED and Yiviva; has served as a consultant or on data and safety monitoring boards (DSMBs) for AbbVie, Arcus, AstraZeneca, Autem Medical, Ability Pharma, Alligator Bioscience, Agenus, Berry Genomics, BioNTech SE, Boehringer Ingelheim, Ipsen, Ikena, Merck, Moma Therapeutics, Novartis, Leap Therapeutics, Astellas, Bristol-Myers Squibb, Revolution Medicines, Regeneron and Tango; and also reports an uncompensated relationship with Thetis Pharma, travel support from BioNTech and Arcus and a disclosed financial relationship between her spouse and AbbVie.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}