Abscopal effects of radiotherapy and combined mRNA-based immunotherapy in a syngeneic, OVA-expressing thymoma mouse model.
BACKGROUND
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®).


METHODS
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.


RESULTS
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.


CONCLUSION
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.
['Basler|Lucas|L|http://orcid.org/0000-0003-1259-5825', 'Kowalczyk|Aleksandra|A|', 'Heidenreich|Regina|R|', 'Fotin-Mleczek|Mariola|M|', 'Tsitsekidis|Savas|S|', 'Zips|Daniel|D|', 'Eckert|Franziska|F|', 'Huber|Stephan M|SM|']
D000818:Animals D000911:Antibodies, Monoclonal D003131:Combined Modality Therapy D004195:Disease Models, Animal D051379:Mice D008810:Mice, Inbred C57BL D010047:Ovalbumin D012333:RNA, Messenger D016499:Radioimmunotherapy D013945:Thymoma D013953:Thymus Neoplasms
Abscopal effects Radiotherapy Immunotherapy Radioimmunotherapy Tumor vaccine mRNA vaccination