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

Oltmanns F, Vieira Antao AI, Irrgang P, Viherlehto V, Jörg L, Schmidt A, Wagner J, Rückert M, Flohr AS, Geppert CI, Frey B, Bayer W, Gravekamp C, Tenbusch M, Gaipl U, Lapuente D (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Journal for ImmunoTherapy of Cancer BioMed Central

Book Volume: 12

Article Number: e008652

Journal Issue: 3

DOI: 10.1136/jitc-2023-008652

Abstract

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.

Authors with CRIS profile

Friederike Oltmanns Institute of Clinical and Molecular Virology Ana Isabel Vieira Antao Institute of Clinical and Molecular Virology Vera Viherlehto Institute of Clinical and Molecular Virology Leticia Jörg Institute of Clinical and Molecular Virology Anna Schmidt Institute of Clinical and Molecular Virology Jannik Wagner Institute of Clinical and Molecular Virology Michael Rückert Department of Radiation Oncology Ann-Sophie Flohr Department of Radiation Oncology Carol-Immanuel Geppert Institute of Pathology Benjamin Frey Department of Radiation Oncology Matthias Tenbusch Professur für Genbasierte Immunisierungsverfahren Udo Gaipl Department of Radiation Oncology Dennis Lapuente Institute of Clinical and Molecular Virology

Involved external institutions

Universitätsklinikum Essen DE Germany (DE) Albert Einstein College of Medicine US United States (USA) (US)

How to cite

APA:

Oltmanns, F., Vieira Antao, A.I., Irrgang, P., Viherlehto, V., Jörg, L., Schmidt, A.,... Lapuente, D. (2024). Mucosal tumor vaccination delivering endogenous tumor antigens protects against pulmonary breast cancer metastases. Journal for ImmunoTherapy of Cancer, 12(3). https://doi.org/10.1136/jitc-2023-008652

MLA:

Oltmanns, Friederike, et al. "Mucosal tumor vaccination delivering endogenous tumor antigens protects against pulmonary breast cancer metastases." Journal for ImmunoTherapy of Cancer 12.3 (2024).

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