Academic Journal
Carbon Ion and Photon Radiation Therapy Show Enhanced Antitumoral Therapeutic Efficacy With Neoantigen RNA-LPX Vaccines in Preclinical Colon Carcinoma Models
| Τίτλος: | Carbon Ion and Photon Radiation Therapy Show Enhanced Antitumoral Therapeutic Efficacy With Neoantigen RNA-LPX Vaccines in Preclinical Colon Carcinoma Models |
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| Συγγραφείς: | Salomon, Nadja, Helm, Alexander, Selmi, Abderaouf, Fournier, Claudia, Diken, Mustafa, Schrörs, Barbara, Scholz, Michael, Kreiter, Sebastian, Durante, Marco, Vascotto, Fulvia |
| Πηγή: | International journal of radiation oncology, biology, physics 119(3), 936-945 (2024). doi:10.1016/j.ijrobp.2023.12.042 |
| Στοιχεία εκδότη: | Elsevier BV, 2024. |
| Έτος έκδοσης: | 2024 |
| Θεματικοί όροι: | Cancer Vaccines: immunology, Immunotherapy: methods, Heavy Ion Radiotherapy, Colonic Neoplasms: immunology, Adenocarcinoma, Cancer Vaccines, Mice, Antigens, Neoplasm, Cell Line, Tumor, Animals, Adenocarcinoma: radiotherapy, RNA, Messenger, mRNA Vaccines: therapeutic use, Adenocarcinoma: immunology, Photons, Antigens, Neoplasm: immunology, Combined Modality Therapy, Combined Modality Therapy: methods, Mice, Inbred C57BL, Colonic Neoplasms: radiotherapy, Colonic Neoplasms, Liposomes, Cancer Vaccines: therapeutic use, Female, Heavy Ion Radiotherapy: methods, Immunotherapy, mRNA Vaccines, Photons: therapeutic use |
| Περιγραφή: | Personalized liposome-formulated mRNA vaccines (RNA-LPX) are a powerful new tool in cancer immunotherapy. In preclinical tumor models, RNA-LPX vaccines are known to achieve potent results when combined with conventional X-ray radiation therapy (XRT). Densely ionizing radiation used in carbon ion radiation therapy (CIRT) may induce distinct effects in combination with immunotherapy compared with sparsely ionizing X-rays.Within this study, we investigate the potential of CIRT and isoeffective doses of XRT to mediate tumor growth inhibition and survival in murine colon adenocarcinoma models in conjunction with neoantigen (neoAg)-specific RNA-LPX vaccines encoding both major histocompatibility complex (MHC) class I- and class II-restricted tumor-specific neoantigens. We characterize tumor immune infiltrates and antigen-specific T cell responses by flow cytometry and interferon-γ enzyme-linked immunosorbent spot (ELISpot) analyses, respectively.NeoAg RNA-LPX vaccines significantly potentiate radiation therapy-mediated tumor growth inhibition. CIRT and XRT alone marginally prime neoAg-specific T cell responses detected in the tumors but not in the blood or spleens of mice. Infiltration and cytotoxicity of neoAg-specific T cells is strongly driven by RNA-LPX vaccines and is accompanied by reduced expression of the inhibitory markers PD-1 and Tim-3 on these cells. The neoAg RNA-LPX vaccine shows similar overall therapeutic efficacy in combination with both CIRT and XRT, even if the physical radiation dose is lower for carbon ions than for X-rays.We hence conclude that the combination of CIRT and neoAg RNA-LPX vaccines is a promising strategy for the treatment of radioresistant tumors. International journal of radiation oncology, biology, physics 119(3), 936 - 945 (2024). doi:10.1016/j.ijrobp.2023.12.042 Published by Elsevier Science, Amsterdam [u.a.] |
| Τύπος εγγράφου: | Article |
| Γλώσσα: | English |
| ISSN: | 0360-3016 |
| DOI: | 10.1016/j.ijrobp.2023.12.042 |
| DOI: | 10.15120/gsi-2024-00796 |
| Σύνδεσμος πρόσβασης: | https://pubmed.ncbi.nlm.nih.gov/38163521 https://repository.gsi.de/record/353131 |
| Rights: | CC BY |
| Αριθμός Καταχώρησης: | edsair.doi.dedup.....e80b4439569218dc63f1cad27ea28c80 |
| Βάση Δεδομένων: | OpenAIRE |
| ISSN: | 03603016 |
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| DOI: | 10.1016/j.ijrobp.2023.12.042 |