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@ARTICLE{Salomon:353131,
author = {Salomon, Nadja and Helm, Alexander and Selmi, Abderaouf and
Fournier, Claudia and Diken, Mustafa and Schrörs, Barbara
and Scholz, Michael and Kreiter, Sebastian and Durante,
Marco and Vascotto, Fulvia},
title = {{C}arbon {I}on and {P}hoton {R}adiation {T}herapy {S}how
{E}nhanced {A}ntitumoral {T}herapeutic {E}fficacy {W}ith
{N}eoantigen {RNA}-{LPX} {V}accines in {P}reclinical {C}olon
{C}arcinoma {M}odels},
journal = {International journal of radiation oncology, biology,
physics},
volume = {119},
number = {3},
issn = {0360-3016},
address = {Amsterdam [u.a.]},
publisher = {Elsevier Science},
reportid = {GSI-2024-00796},
pages = {936 - 945},
year = {2024},
note = {This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/)},
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.},
keywords = {Animals / Colonic Neoplasms: radiotherapy / Colonic
Neoplasms: immunology / Mice / Cancer Vaccines: therapeutic
use / Cancer Vaccines: immunology / Antigens, Neoplasm:
immunology / Heavy Ion Radiotherapy: methods / Photons:
therapeutic use / Female / Adenocarcinoma: radiotherapy /
Adenocarcinoma: immunology / Combined Modality Therapy:
methods / Liposomes / mRNA Vaccines: therapeutic use / Cell
Line, Tumor / Immunotherapy: methods / RNA, Messenger /
Mice, Inbred C57BL / Cancer Vaccines (NLM Chemicals) /
Antigens, Neoplasm (NLM Chemicals) / Liposomes (NLM
Chemicals) / mRNA Vaccines (NLM Chemicals) / RNA, Messenger
(NLM Chemicals)},
cin = {BIO / BIO@FAIR},
ddc = {610},
cid = {I:(DE-Ds200)BIO-20160831OR354 / I:(DE-Ds200)Coll-FAIR-BIO},
pnm = {633 - Life Sciences – Building Blocks of Life: Structure
and Function (POF4-633) / SUC-GSI-Darmstadt - Strategic
university cooperation GSI-TU Darmstadt (SUC-GSI-DA) / FAIR
Phase-0 - FAIR Phase-0 Research Program (GSI-FAIR-Phase-0)},
pid = {G:(DE-HGF)POF4-633 / G:(DE-Ds200)SUC-GSI-DA /
G:(Ds200)GSI-FAIR-Phase-0},
experiment = {$EXP:(DE-Ds200)SBio08_Salomon-20200803$},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38163521},
UT = {WOS:001263754200001},
doi = {10.1016/j.ijrobp.2023.12.042},
url = {https://repository.gsi.de/record/353131},
}