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

作者：Basler Lucas^*; Kowalczyk Aleksandra; Heidenreich Regina; Fotin Mleczek Mariola; Tsitsekidis Savas; Zips Daniel; Eckert Franziska; Huber Stephan M

来源：Cancer Immunology, Immunotherapy, 2018, 67(4): 653-662.

DOI：10.1007/s00262-018-2117-0

• Abscopal effects
• Immunotherapy
• Radiotherapy
• Tumor vaccine
• Radioimmunotherapy
• mRNA vaccination

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 (R)).
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 x 2 Gy, while secondary tumors were shielded. RNA and combined treatment groups received mRNA-based RNActive (R) 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.

• 出版日期2018-4