Adoptive cell transfer (ACT) has shown promising results in clinical trials for melanoma, with response rates ranging from 40% to 72%. We aimed to enhance the efficacy of ACT by coupling it with adenoviruses coding for immunostimulatory cytokines. The non-replicating adenoviruses that were constructed (Ad5-CMV-mIFNg, Ad5-CMV-mIL2, Ad5-CMV-mIFNb and Ad5-CMV-mTNFa) were confirmed to produce biologically active murine cytokines in vitro. These viruses were then used in combination with adoptive transfer of OT-1 TCR transgenic T-cells to treat C57BL/6 mice bearing B16-OVA melanoma tumors. The animals were administered intraperitoneally with 1.5 x 106 CD8+-enriched OT-1 cells with or without intratumoral injections of cytokine-coding adenoviruses (1 x 109 viral particles/tumor). Combination treatment with Ad5-CMV-mIL2 and OT-1 resulted in statistically significant antitumor efficacy when compared with either monotherapy and untreated control (combination vs. virus, p=0.026; combination vs. OT1, p=0.003; combination vs. mock, p<0.001). Similar results were obtained with other cytokine-coding virus and OT-1 combinations, except for mIFNb. In further experiments a triple combination of Ad5-CMV-mIL2 + Ad5-CMV-mTNFa (1:1 ratio) and OT-1 T-cells were used to treat B16-OVA; improved antitumor efficacy was observed with the triple combination over dual agent therapies (triple combination vs. Ad5-CMV-mIL2 + OT-1, p=0.001; triple combination vs. Ad5-CMV-mTNFa + OT-1, p=0.049). In summary, these results support the further development of a novel immunotherapeutic approach for the treatment of melanoma.
Citation Format: Mikko Siurala, Riikka Havunen, Simona Bramante, Dipongkor Saha, Siri Tähtinen, Markus Vähä-Koskela, Akseli Hemminki. Adoptive T-cell transfer combined with murine cytokine-armed adenoviruses for the treatment of melanoma. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy: A New Chapter; December 1-4, 2014; Orlando, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2015;3(10 Suppl):Abstract nr B18.
- ©2015 American Association for Cancer Research.