Description

Combination therapy of flagellin-adjuvanted cancer vaccine and radiotherapy induces long-term protection in a mouse cervical cancer model

Shee Eun Lee¹, Seol Hee Hong¹, Hye Hwa Lee¹, Kwangjoon Jeong¹, Tan Wenzhi¹, Mee Sun Yoon², In-Kyu Park¹, Jung-Joon Min¹, Joon Haeng Rhee¹

¹Clinical Vaccine R&D Center, Chonnam National University, Gwangju, Republic of Korea;

²Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea

Accumulating evidence demonstrates that radiotherapy enhances anti-tumor immune responses induced by immunomodulatory therapeutic approaches. Radiotherapy (RT) is widely used cost-effective therapeutics for the various cancers having accompanying adverse effect. Recently it has been reported that flagellin derivatives significantly reduced the severity of radiation-induced side effect and accelerated tissue recovery. We previously demonstrated that flagellin potentiates tumor antigen-specific CD8⁺ T cell immune responses through TLR5 signaling in a TC-1 cancer immunotherapy (IT) model. And intravaginal (IVAG) co-administration of E6/E7 peptides with flagellin resulted in tumor suppression indicating flagellin is a potent vaginal adjuvant for a therapeutic peptide cancer vaccine. In this regard, we examined whether flagellin can be used as an adjuvant performing dual role of radioprotection and immunomodulation in an RT/IT combinatorial cervical cancer therapeutic model. When the tumor-bearing mice (5 ~8 mm in mean diameter) were locally received 20 Gy single dose irradiation, tumor growth was significantly reduced. Additional administration of flagellin-adjuvanted peptide vaccine showed comparable inhibitory effect on tumor growth. Surprisingly the combination therapy of flagellin-adjuvanted cancer vaccine and radiotherapy induced eradication of tumor mass and long-term memory protection against the re-challenge of the same tumor. These results suggest that flagellin is a promising radioprotective adjuvant for RT/IT combination therapeutics modalities against intractable cancers.