Hauptseite > Publikationsdatenbank > Carbon Ion and Photon Radiation Therapy Show Enhanced Antitumoral Therapeutic Efficacy With Neoantigen RNA-LPX Vaccines in Preclinical Colon Carcinoma Models > print

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005     20250717224050.0
024 7 _ |a 10.1016/j.ijrobp.2023.12.042
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024 7 _ |a 0360-3016
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024 7 _ |a 1879-355X
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024 7 _ |a 10.15120/GSI-2024-00796
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100 1 _ |a Salomon, Nadja
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245 _ _ |a Carbon Ion and Photon Radiation Therapy Show Enhanced Antitumoral Therapeutic Efficacy With Neoantigen RNA-LPX Vaccines in Preclinical Colon Carcinoma Models
260 _ _ |a Amsterdam [u.a.]
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|b Elsevier Science
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500 _ _ |a This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
520 _ _ |a 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.
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650 _ 7 |a Cancer Vaccines
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650 _ 7 |a Antigens, Neoplasm
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650 _ 7 |a Liposomes
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650 _ 7 |a mRNA Vaccines
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650 _ 7 |a RNA, Messenger
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650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Colonic Neoplasms: radiotherapy
|2 MeSH
650 _ 2 |a Colonic Neoplasms: immunology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Cancer Vaccines: therapeutic use
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650 _ 2 |a Cancer Vaccines: immunology
|2 MeSH
650 _ 2 |a Antigens, Neoplasm: immunology
|2 MeSH
650 _ 2 |a Heavy Ion Radiotherapy: methods
|2 MeSH
650 _ 2 |a Photons: therapeutic use
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Adenocarcinoma: radiotherapy
|2 MeSH
650 _ 2 |a Adenocarcinoma: immunology
|2 MeSH
650 _ 2 |a Combined Modality Therapy: methods
|2 MeSH
650 _ 2 |a Liposomes
|2 MeSH
650 _ 2 |a mRNA Vaccines: therapeutic use
|2 MeSH
650 _ 2 |a Cell Line, Tumor
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650 _ 2 |a Immunotherapy: methods
|2 MeSH
650 _ 2 |a RNA, Messenger
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650 _ 2 |a Mice, Inbred C57BL
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700 1 _ |a Helm, Alexander
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773 _ _ |a 10.1016/j.ijrobp.2023.12.042
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