Mucosal tumor vaccination delivering endogenous tumor antigens protects against pulmonary breast cancer metastases.

Autor:	Oltmanns F; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Vieira Antão A; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Irrgang P; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Viherlehto V; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Jörg L; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Schmidt A; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Wagner JT; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Rückert M; Translational Radiobiology, Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Flohr AS; Translational Radiobiology, Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Geppert CI; Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.; Comprehensive Cancer Center Erlangen-EMN (CCC), University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany., Frey B; Translational Radiobiology, Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.; FAU Profile Center Immunomedicine (FAU I-MED), Friedrich-Alexander-Universität Erlangen-Nuremberg, Erlangen, Germany., Bayer W; Institute for Virology, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Gravekamp C; Department of Microbiology & Immunology, Albert Einstein College of Medicine, New York, New York, USA., Tenbusch M; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.; FAU Profile Center Immunomedicine (FAU I-MED), Friedrich-Alexander-Universität Erlangen-Nuremberg, Erlangen, Germany., Gaipl U; Translational Radiobiology, Department of Radiation Oncology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.; FAU Profile Center Immunomedicine (FAU I-MED), Friedrich-Alexander-Universität Erlangen-Nuremberg, Erlangen, Germany., Lapuente D; Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany Dennis.Lapuente@uk-erlangen.de.
Jazyk:	angličtina
Zdroj:	Journal for immunotherapy of cancer [J Immunother Cancer] 2024 Mar 07; Vol. 12 (3). Date of Electronic Publication: 2024 Mar 07.
DOI:	10.1136/jitc-2023-008652
Abstrakt:	Background: Generally, early-stage breast cancer has a good prognosis. However, if it spreads systemically, especially with pulmonary involvement, prospects worsen dramatically. Importantly, tumor-infiltrating T cells contribute to tumor control, particularly intratumoral T cells with a tissue-resident memory phenotype are associated with an improved clinical outcome. Methods: Here, we use an adenoviral vector vaccine encoding endogenous tumor-associated antigens adjuvanted with interleukin-1β to induce tumor-specific tissue-resident memory T cells (TRM) in the lung for the prevention and treatment of pulmonary metastases in the murine 4T1 breast cancer model. Results: The mucosal delivery of the vaccine was highly efficient in establishing tumor-specific TRM in the lung. Concomitantly, a single mucosal vaccination reduced the growth of pulmonary metastases and improved the survival in a prophylactic treatment. Vaccine-induced TRM contributed to these protective effects. In a therapeutic setting, the vaccination induced a pronounced T cell infiltration into metastases but resulted in only a minor restriction of the disease progression. However, in combination with stereotactic radiotherapy, the vaccine increased the survival time and rate of tumor-bearing mice. Conclusion: In summary, our study demonstrates that mucosal vaccination is a promising strategy to harness the power of antitumor TRM and its potential combination with state-of-the-art treatments. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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