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000353131 1001_ $$0P:(DE-HGF)0$$aSalomon, Nadja$$b0$$eCorresponding author
000353131 245__ $$aCarbon Ion and Photon Radiation Therapy Show Enhanced Antitumoral Therapeutic Efficacy With Neoantigen RNA-LPX Vaccines in Preclinical Colon Carcinoma Models
000353131 260__ $$aAmsterdam [u.a.]$$bElsevier Science$$c2024
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000353131 500__ $$a This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
000353131 520__ $$aPersonalized 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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000353131 650_7 $$2NLM Chemicals$$aCancer Vaccines
000353131 650_7 $$2NLM Chemicals$$aAntigens, Neoplasm
000353131 650_7 $$2NLM Chemicals$$aLiposomes
000353131 650_7 $$2NLM Chemicals$$amRNA Vaccines
000353131 650_7 $$2NLM Chemicals$$aRNA, Messenger
000353131 650_2 $$2MeSH$$aAnimals
000353131 650_2 $$2MeSH$$aColonic Neoplasms: radiotherapy
000353131 650_2 $$2MeSH$$aColonic Neoplasms: immunology
000353131 650_2 $$2MeSH$$aMice
000353131 650_2 $$2MeSH$$aCancer Vaccines: therapeutic use
000353131 650_2 $$2MeSH$$aCancer Vaccines: immunology
000353131 650_2 $$2MeSH$$aAntigens, Neoplasm: immunology
000353131 650_2 $$2MeSH$$aHeavy Ion Radiotherapy: methods
000353131 650_2 $$2MeSH$$aPhotons: therapeutic use
000353131 650_2 $$2MeSH$$aFemale
000353131 650_2 $$2MeSH$$aAdenocarcinoma: radiotherapy
000353131 650_2 $$2MeSH$$aAdenocarcinoma: immunology
000353131 650_2 $$2MeSH$$aCombined Modality Therapy: methods
000353131 650_2 $$2MeSH$$aLiposomes
000353131 650_2 $$2MeSH$$amRNA Vaccines: therapeutic use
000353131 650_2 $$2MeSH$$aCell Line, Tumor
000353131 650_2 $$2MeSH$$aImmunotherapy: methods
000353131 650_2 $$2MeSH$$aRNA, Messenger
000353131 650_2 $$2MeSH$$aMice, Inbred C57BL
000353131 693__ $$0EXP:(DE-Ds200)SBio08_Salomon-20200803$$1EXP:(DE-Ds200)HTM-20200803$$5EXP:(DE-Ds200)SBio08_Salomon-20200803$$aHTM$$eSBio08_Salomon: Combined carbon ion radiotherapy and cancer vaccines in a subcutaneous murine MC38 adenocarcinoma model (POF3-315; HTM )$$x0
000353131 7001_ $$0P:(DE-Ds200)OR3001$$aHelm, Alexander$$b1$$ugsi
000353131 7001_ $$0P:(DE-HGF)0$$aSelmi, Abderaouf$$b2
000353131 7001_ $$0P:(DE-Ds200)OR0311$$aFournier, Claudia$$b3$$ugsi
000353131 7001_ $$0P:(DE-HGF)0$$aDiken, Mustafa$$b4
000353131 7001_ $$0P:(DE-HGF)0$$aSchrörs, Barbara$$b5
000353131 7001_ $$0P:(DE-Ds200)OR1138$$aScholz, Michael$$b6$$ugsi
000353131 7001_ $$0P:(DE-HGF)0$$aKreiter, Sebastian$$b7
000353131 7001_ $$0P:(DE-Ds200)OR2413$$aDurante, Marco$$b8$$ugsi
000353131 7001_ $$0P:(DE-HGF)0$$aVascotto, Fulvia$$b9
000353131 773__ $$0PERI:(DE-600)1500486-7$$a10.1016/j.ijrobp.2023.12.042$$gVol. 119, no. 3, p. 936 - 945$$n3$$p936 - 945$$tInternational journal of radiation oncology, biology, physics$$v119$$x0360-3016$$y2024
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