Abscopal effects of radiotherapy and combined mRNA-based immunotherapy in a syngeneic, OVA-expressing thymoma mouse model
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Tumor metastasis and immune evasion present major challenges of cancer treatment. Radiotherapy can overcome immunosuppressive tumor microenvironments. Anecdotal reports suggest abscopal anti-tumor immune responses. This study assesses abscopal effects of radiotherapy in combination with mRNA-based cancer vaccination (RNActive®).
C57BL/6 mice were injected with ovalbumin-expressing thymoma cells into the right hind leg (primary tumor) and left flank (secondary tumor) with a delay of 4 days. Primary tumors were irradiated with 3 × 2 Gy, while secondary tumors were shielded. RNA and combined treatment groups received mRNA-based RNActive® vaccination.
Radiotherapy and combined radioimmunotherapy significantly delayed primary tumor growth with a tumor control in 15 and 53% of mice, respectively. In small secondary tumors, radioimmunotherapy significantly slowed growth rate compared to vaccination (p = 0.002) and control groups (p = 0.01). Cytokine microarray analysis of secondary tumors showed changes in the cytokine microenvironment, even in the non-irradiated contralateral tumors after combination treatment.
Combined irradiation and immunotherapy is able to induce abscopal responses, even with low, normofractionated radiation doses. Thus, the combination of mRNA-based vaccination with irradiation might be an effective regimen to induce systemic anti-tumor immunity.
KeywordsAbscopal effects Immunotherapy Radiotherapy Tumor vaccine Radioimmunotherapy mRNA vaccination
Biologically effective dose
Danger-associated molecular pattern
Vascular endothelial growth factor
LB conducted the experiments and wrote the manuscript. AK helped with the experiments. RH revised the manuscript. MFM helped with the experiments. ST performed the dosimetry experiments. DZ revised the manuscript. FE wrote the manuscript. SMH designed the experiments and revised the manuscript.
Lucas Basler was funded by a grant of the IZKF Promotionskolleg (Interdisziplinäres Zentrum für Klinische Forschung, Interdisciplinary Centre for Clinical Research, University of Tübingen). Franziska Eckert was partly funded by the Else-Kroener-Fresenius research grant “Therapy resistance of solid tumors” (2015_Kolleg.14).
Compliance with ethical standards
Conflict of interest
Aleksandra Kowalczyk, Regina Heidenreich, and Mariola Fotin-Mleczek were employees of CureVac AG at the time of the experiments’ performance or preparation of the manuscript. The others authors declare that they have no conflict of interest.
All procedures performed in studies involving animals were in accordance with the animal protection laws and regulations, and were approved by the local authorities.
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