Exploiting host pre-existing immunity for melanoma cancer immunotherapy

Vaccines are considered one of greatest successes of modern medicine; indeed, prophylactic vaccinations allow tight control of disease spreading and even eradication of some diseases. Vaccines immunize patients against known antigens derived from infectious agents, so that the immune system can efficiently block pathogen entry and mount a faster and better immune reaction in case of infection. In the context of cancer, finding good antigens for immunization against tumor cells can be challenging since tumor cells are derived from the self, and thus are not always efficiently recognized as malignant by the immune system. Here, we seek to develop a cancer immunotherapy that delivers a pre-encountered antigen to tumor cells to redirect the host pre-existing immunity against cancer. As a vaccine model, we used ovalbumin (OVA) antigen adjuvanted with CpG-B oligodeoxynucleotides to pre-immunize C57BL/6 mice, developing both T cell and B cell immunity against OVA. At least one month later, mice were challenged with B16-OVA melanoma cells. We observed that tumor growth in pre-immunized mice was slightly delayed compared to growth in naive mice, but this effect was modest, leading to an overall 1-day increased survival. We reasoned that this effect could be improved by modifying the cellular localization of OVA antigen; indeed, OVA is expressed intracellularly in B16-OVA cells, thus excluding potential antibody-mediated anti-tumoral immune response. Therefore, we created a B16 melanoma cell line that overexpresses a membrane-bound OVA (B16memOVA), using similar design as published elsewhere (DiLillo et al., J. Immunol. 2010). In vitro, B16memOVA cells behaved similarly to the parental B16 cell line, and the growth of B16memOVA tumors in OVA-expressing mice (which are tolerant to OVA) was similar to the growth of B16 tumors, thus validating our B16memOVA tumor model. When implanted in naive mice, B16memOVA tumors were able to grow, despite the onset of a neo-immune reaction against OVA, which slows tumor growth. In contrast, mice pre-immunized against OVA totally rejected B16memOVA tumors. Our efforts are now focusing on the development of an antigen-delivery method to trigger the expression of membrane-bound OVA in B16 tumors after implantation, to apply this approach in a therapeutic setup. Citation Format: Priscilla S. Briquez, Sylvie Hauert, Gregoire Repond, Melody A. Swartz, Jeffrey A. Hubbell. Exploiting host pre-existing immunity for melanoma cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1217.