Journal Article

GSI-2024-00796

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Carbon Ion and Photon Radiation Therapy Show Enhanced Antitumoral Therapeutic Efficacy With Neoantigen RNA-LPX Vaccines in Preclinical Colon Carcinoma Models

Salomon, N. (Corresponding author) ; Helm, A.GSI* ; Selmi, A. ; Fournier, C.GSI* ; Diken, M. ; Schrörs, B. ; Scholz, M.GSI* ; Kreiter, S. ; Durante, M.GSI* ; Vascotto, F.

2024
Elsevier Science Amsterdam [u.a.]

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Please use a persistent id in citations: doi:10.1016/j.ijrobp.2023.12.042  doi:10.15120/GSI-2024-00796

Abstract: 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.

Keyword(s): Animals (MeSH) ; Colonic Neoplasms: radiotherapy (MeSH) ; Colonic Neoplasms: immunology (MeSH) ; Mice (MeSH) ; Cancer Vaccines: therapeutic use (MeSH) ; Cancer Vaccines: immunology (MeSH) ; Antigens, Neoplasm: immunology (MeSH) ; Heavy Ion Radiotherapy: methods (MeSH) ; Photons: therapeutic use (MeSH) ; Female (MeSH) ; Adenocarcinoma: radiotherapy (MeSH) ; Adenocarcinoma: immunology (MeSH) ; Combined Modality Therapy: methods (MeSH) ; Liposomes (MeSH) ; mRNA Vaccines: therapeutic use (MeSH) ; Cell Line, Tumor (MeSH) ; Immunotherapy: methods (MeSH) ; RNA, Messenger (MeSH) ; Mice, Inbred C57BL (MeSH) ; Cancer Vaccines ; Antigens, Neoplasm ; Liposomes ; mRNA Vaccines ; RNA, Messenger

Note: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

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Contributing Institute(s):

1. Biophysik (BIO)
2. Collaboration FAIR: BIO (BIO@FAIR)

Research Program(s):

1. 633 - Life Sciences – Building Blocks of Life: Structure and Function (POF4-633) (POF4-633)
2. SUC-GSI-Darmstadt - Strategic university cooperation GSI-TU Darmstadt (SUC-GSI-DA) (SUC-GSI-DA)
3. FAIR Phase-0 - FAIR Phase-0 Research Program (GSI-FAIR-Phase-0) (GSI-FAIR-Phase-0)

Experiment(s):

1. SBio08_Salomon: Combined carbon ion radiotherapy and cancer vaccines in a subcutaneous murine MC38 adenocarcinoma model (POF3-315; HTM )

Appears in the scientific report 2024

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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