CoChat
Sign Up
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

Published version of a preprint

Open this paper in CoChat — free account

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

Overview

Integrity signals

Registry

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

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 45 references

Cited by

Sorted by citations

Related

See all

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review