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Cited by 124Immunotherapy and Immune ResponsesCancer Immunotherapy and BiomarkersCAR-T cell therapy research

The DOI matches its Crossref record; 44 of the 45 references it cites were found in a registry or an index.

T-cell Responses to Individualized Neoantigen Therapy mRNA-4157 (V940) Alone or in Combination with Pembrolizumab in the Phase 1 KEYNOTE-603 Study

Gainor, Justin F., Patel, Manish R., Weber, Jeffrey S., Gutierrez, Martin, Bauman, Julie E., Clarke, Jeffrey M., Julian, Ricklie, Scott, Aaron J., Geiger, Jessica L., Kirtane, Kedar, Robert-Tissot, Celine, Coder, Brandon, Tasneem, Moomal, Sun, Jing, Zheng, Wei, Gerbereux, Lauren, Laino, Andressa, Porichis, Filippos, Pollard, Jack Russella, Hou, Peijie, Sehgal, Vasudha, Chen, Xing, Morrissey, Manju, Daghestani, Hikmat N., Feldman, Igor, Srinivasan, Lakshmi, Frederick, Joshua P., Brown, Michelle, Aanur, Praveen, Meehan, Robert, Burris, Howard A.·2024·Cancer Discovery
DOI 10.1158/2159-8290.cd-24-0158

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Abstract

mRNA-4157 (V940) is an individualized neoantigen therapy targeting up to 34 patient-specific tumor neoantigens to induce T-cell responses and potentiate antitumor activity. We report mechanistic insights into the immunogenicity of mRNA-4157 via characterization of T-cell responses to neoantigens from the first-in-human, phase 1, KEYNOTE-603 study (NCT03313778) in patients with resected non–small cell lung cancer (Part A: 1-mg mRNA-4157, n = 4) or resected cutaneous melanoma (Part D: 1-mg mRNA-4157 + 200-mg pembrolizumab, n = 12). Safety, tolerability, and immunogenicity were assessed. All patients experienced ≥1 treatment-emergent adverse event; there were no grade 4/5 adverse events or dose-limiting toxicities. mRNA-4157 alone induced consistent de novo and strengthened preexisting T-cell responses to targeted neoantigens. Following combination therapy, sustained mRNA-4157-induced neoantigen-specific T-cell responses and expansion of cytotoxic CD8 and CD4 T cells were observed. These findings show the potential of a novel mRNA individualized neoantigen therapy approach in oncology. Significance: The safety and immunogenicity results from this phase 1 study of mRNA-4157 as adjuvant monotherapy or combination therapy with pembrolizumab show generation of de novo and enhancement of existing neoantigen-specific T-cell responses and provide mechanistic proof of concept to support further development of mRNA-4157 for patients with resected solid tumors. See related commentary by Berraondo et al., p. 2021

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Crossref · 10.1158/2159-8290.cd-24-0158

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Metadata

Authors
Gainor, J. F., Patel, M. R., Weber, J. S., Gutierrez, M., Bauman, J. E., Clarke, J. M., Julian, R., Scott, A. J., Geiger, J. L., Kirtane, K., Robert-Tissot, C., Coder, B., Tasneem, M., Sun, J., Zheng, W., Gerbereux, L., Laino, A., Porichis, F., Pollard, J. R., Hou, P., Sehgal, V., Chen, X., Morrissey, M., Daghestani, H. N., Feldman, I., Srinivasan, L., Frederick, J. P., Brown, M., Aanur, P., Meehan, R., & Burris, H. A.
Affiliations
  • Massachusetts General Hospital (US)
  • Sarah Cannon (US)
  • NYU Langone Health (US)
  • Hackensack University Medical Center (US)
  • George Washington University (US)
  • Duke University (US)
  • University of Arizona Cancer Center (US)
  • Banner - University Medical Center Tucson (US)
  • Cleveland Clinic (US)
  • Moffitt Cancer Center (US)
  • 11Moderna, Inc., Cambridge, Massachusetts.
  • Moderna Therapeutics (United States) (US)
  • HiFiBiO Therapeutics (United States) (US)
ORCID
Venue
Cancer Discovery
Publisher
American Association for Cancer Research (AACR)
Published
2024-08-08
Volume
14
Issue
11
Pages
2209-2223
ISSN
  • 2159-8274 (ISSN-L)
  • 2159-8290
DOI
10.1158/2159-8290.cd-24-0158
OpenAlex
W4401422221
Cited by
124
References
45
Citations by year
2026: 58 · 2025: 63 · 2024: 3
FWCI
20.74
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Discovery (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Health Sciences › Medicine › Oncology › CAR-T cell therapy research
Keywords
neoantigens, T cell response, pembrolizumab, non-small cell lung cancer, cutaneous melanoma, mRNA vaccines, immunogenicity, CD8+ T cells, CD4+ T cells, adjuvant therapy
MeSH terms
Antineoplastic Agents, Immunological, Adult, Aged, Antigens, Neoplasm, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Melanoma, Middle Aged, Skin Neoplasms, T-Lymphocytes, Precision Medicine, Antibodies, Monoclonal, Humanized

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