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

Abstract

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.

• Authors: Lucas Basler, Aleksandra Kowalczyk, Regina Heidenreich, Mariola Fotin-Mleczek, Savas Tsitsekidis, Daniel Zips, Franziska Eckert, Stephan M Huber
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 67 Issue 4 Pg. 653-662 (Apr 2018) ISSN: 1432-0851 [Electronic] Germany
• PMID: 29335856 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• RNA, Messenger
• Ovalbumin

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage)
• Combined Modality Therapy
• Disease Models, Animal
• Mice
• Mice, Inbred C57BL
• Ovalbumin (genetics, immunology)
• RNA, Messenger (genetics, immunology)
• Radioimmunotherapy
• Thymoma (genetics, immunology, therapy)
• Thymus Neoplasms (genetics, immunology, therapy)