Chandelier
Senior Member (Voting Rights)
I‘m not sure if this will be the final name of the study.
Abstract found via 2025 European Society for Medical Oncology (ESMO) Congress:
cslide.ctimeetingtech.com
We hypothesized that mRNA vaccines targeting non-tumor antigens, such as those targeting SARS-CoV-2 spike protein, would also sensitize tumors to ICIs.
We evaluated differences with Kaplan-Meier curves, propensity score matching and cox proportional hazards regression.
We then utilized mouse models and samples from healthy human subjects for mechanistic studies.
All experiments were approved by the MD Anderson institutional review board and IACUC.
Survival benefits were maintained with propensity score matching and among patients with immunologically “cold” tumors (TPS<1%).
In preclinical models, SARS-CoV-2 mRNA vaccination stimulated a surge in Type I interferon that prompted antigen presenting cells to prime CD8 T cells targeting multiple tumor antigens and tumor cells to upregulate PD-L1 expression.
Combination therapy enhanced responses to ICIs in multiple tumor models. SARS-CoV-2 mRNA vaccination was associated with similar increases in Type I interferon and APC activation in human subjects, and increased PD-L1 expression on tumor biopsies from a diverse cohort of cancer patients.
Abstract found via 2025 European Society for Medical Oncology (ESMO) Congress:
ESMO Congress 2025 - Conference Calendar - ESMO Congress 2025
cslide.ctimeetingtech.com
- Adam J. Grippin (Houston, United States of America)
- Christiano Marconi (Gainesville, United States of America)
- Sage Copling (Houston, United States of America)
- Nan Li (Houston, United States of America)
- Chen Braun (Houston, United States of America)
- Cole Woody (Houston, United States of America)
- Elliana Young (Houston, United States of America)
- Priti Gupta (Houston, United States of America)
- D3CODE Team (Houston, United States of America)
- Ryan Sun (Houston, United States of America)
- Padmanee Sharma (Houston, United States of America)
- Jianjun Zhang (Houston, United States of America)
- Don Gibbons (Houston, United States of America)
- Jennifer Wargo (Houston, United States of America)
- Yon Son Betty Kim (Houston, United States of America)
- John Heymach (Houston, United States of America)
- Hector Mendez-Gomez (Gainesville, United States of America)
- Wen Jiang (Houston, United States of America)
- Elias Sayour (Houston, United States of America)
- Steven H. Lin (Houston, United States of America)
Background
mRNA cancer vaccines sensitize tumors to immune checkpoint inhibitors (ICIs) in part by stimulating a surge in inflammatory cytokines.We hypothesized that mRNA vaccines targeting non-tumor antigens, such as those targeting SARS-CoV-2 spike protein, would also sensitize tumors to ICIs.
Methods
We extracted clinical data from institutional databases for patients with non-small cell lung cancer (NSCLC) with biopsies between January 2017 and September 2022, melanoma treated with ICIs between January 2019 and December 2022, and any tumor histology with biopsy samples evaluating PD-L1 from January 2020 to October 2023.We evaluated differences with Kaplan-Meier curves, propensity score matching and cox proportional hazards regression.
We then utilized mouse models and samples from healthy human subjects for mechanistic studies.
All experiments were approved by the MD Anderson institutional review board and IACUC.
Results
Administration of a SARS-CoV-2 mRNA vaccine within 100 days of initiating ICI was associated with increased overall survival among patients with NSCLC (median OS 20.6 months vs. 37.3 months, three-year OS 30.6% vs 55.8%, adj HR 0.51, 95% CI 0.37-0.71, p < 0.0001) and metastatic melanoma (median OS 26.67 months vs unmet, 36-month OS 44.1% vs 67.5%, adj HR 0.34, 95% CI 0.17-0.69, p=0.0029).Survival benefits were maintained with propensity score matching and among patients with immunologically “cold” tumors (TPS<1%).
In preclinical models, SARS-CoV-2 mRNA vaccination stimulated a surge in Type I interferon that prompted antigen presenting cells to prime CD8 T cells targeting multiple tumor antigens and tumor cells to upregulate PD-L1 expression.
Combination therapy enhanced responses to ICIs in multiple tumor models. SARS-CoV-2 mRNA vaccination was associated with similar increases in Type I interferon and APC activation in human subjects, and increased PD-L1 expression on tumor biopsies from a diverse cohort of cancer patients.
Conclusions
SARS-CoV-2 mRNA vaccines sensitize tumors to ICIs in preclinical models and are associated with substantial improvements to overall survival among patients with NSCLC and melanoma treated with ICIs.Research reported in this publication was supported by the National Cancer (NCI) Institute under the University of Texas MD Anderson Cancer Center SPORE in Melanoma P50CA221703, the University of Texas MD Anderson Cancer Center Support Grant P30CA016672, T32-CA196561-08 (A.J.G), R37CA251978 (E.J.S.), and R01CA266857 (E.J.S.). This research was also supported by an FDA orphan disease award R01FD007268 (E.J.S.), foundation grants from the American Brain Tumor Association, the Radiological Society of North America, Conquer Cancer Foundation, CureSearch (Catapult Award), Stop Children’s Cancer and the Bonnie R. Freeman Professorship, Danny’s Dream, Ian’s Friend’s Foundation, Alex’s Lemonade Stand (R Accelerated Award), the Medulloblastoma Initiative (MBI) and Cure Group 4 medulloblastoma consortium, The National Pediatric Cancer Foundation, and generous philanthropic contributions to The University of Texas MD Anderson Lung Moon Shot Program. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding sources including the National Cancer Institute.
Disclosure
A.J. Grippin: Financial Interests, Personal, Invited Speaker: Alamar Biosciences; Financial Interests, Personal, Other, Scientific Advisor: Sift Biosciences; Other, Other, Inventor on patents related to RNA therapeutics.: The University of Texas MD Anderson Cancer Center; Other, Other, Inventor on patents related to RNA therapeutics: University of Florida. P. Sharma: Financial Interests, Personal, Other, Consulting or Stock Ownership or Advisory Board: Achelois, Adaptive Biotechnologies, Phenomic AI, PBM Capital, Oncolytics, Marker, Lytix, Lava Therapeutics, Polaris Pharma, JSL Health, Infinity Pharma, ImaginAb, Hummingbird, Glympse, Earli, Dragonfly, Catalio, BioNTech, BioAtla, Apricity, Sporos, Time Bioventures, Venn Biosciences; Financial Interests, Personal, Advisory Board, Consulting or Stock Ownership or Advisory Board: Akoya Biosciences, Asher Bio, Candel Therapeutics, C-Reveal Therapeutics, Dragonfly Therapeutics, Enable Medicine, Henlius/Hengenix, Matrisome, Neuvogen, NTx, Osteologic, Soley Therapeutics, Spotlight, Trained Therapeutix Discovery, Two Bear Capital, Vironexis, Xilis Inc. J. Zhang: Financial Interests, Personal, Invited Speaker: BeiGene, Johnson and Johnson, Roche, Takeda, Varian; Financial Interests, Institutional, Other, Trial support: Merck; Financial Interests, Personal, Advisory Board, Also supports trial: Novartis, Helius; Financial Interests, Personal, Advisory Board: Oncohost; Financial Interests, Institutional, Other, Supports trial: Summit. J. Wargo: Financial Interests, Personal, Invited Speaker: PeerView; Other, Other, J.A.W. is an inventor on a US patent application (PCT/US17/53.717) submitted by the University of Texas MD Anderson Cancer Center which covers methods to enhance immune checkpoint blockade responses by modulating the microbiome: University of Texas MD Anderson Cancer Center. J. Heymach: Financial Interests, Personal, Advisory Board: Genentech, Mirati Therapeutics, Eli Lilly, Janssen, Boehringer Ingelheim, Regeneron, Takeda, BerGenBio, Jazz, Curio Science, Novartis, AstraZeneca, BioAlta, Sanofi, Spectrum, GSK, EMD Serono, BluePrint Medicine, Chugai, BioNTech; Financial Interests, Personal, Principal Investigator, International PI for clinical trials: AstraZeneca, Boehringer Ingelheim; Financial Interests, Personal and Institutional, Other, Developed a drug: Spectrum; Financial Interests, Personal, Research Funding: Mirati, Bristol Myers Squibb; Financial Interests, Personal, Coordinating PI: Takeda; Financial Interests, Personal, Licencing Fees or royalty for IP: Spectrum; Financial Interests, Personal, Full or part-time Employment: The University of Texas MD Anderson Cancer Center. H. Mendez-Gomez: Financial Interests, Personal, Licencing Fees or royalty for IP: iOncology. E. Sayour: Financial Interests, Personal, Licencing Fees or royalty for IP: iOncology; Financial Interests, Personal, Advisory Role: Siren; Financial Interests, Personal, Advisory Board: Nature's Toolbox, iOncology; Financial Interests, Personal, Stocks or ownership: NTx Bio. S.H. Lin: Financial Interests, Personal, Research Funding: BeyondSpring Pharmaceuticals; Financial Interests, Institutional, Research Funding: Nektar Therpaeutics; Financial Interests, Personal, Other: XRAD Therapeutics; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Varian Medical Systems; Financial Interests, Personal, Full or part-time Employment: The University of Texas MD Anderson Cancer Center; Financial Interests, Personal, Ownership Interest, Co-founder and scientific advisor: Seek Diagnostics; Financial Interests, Personal, Research Grant: STCube Pharmaceuticals; Financial Interests, Personal, Leadership Role, Co-chair RTDT Committee: NRG Oncology. All other authors have declared no conflicts of interest.
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