Abstract 4574: A novel method for inactivating tumor cells for use in a personalized cancer vaccine

Abstract

Abstract With the recent interest in personalized medicine for cancer patients and immune therapy, the field of cancer vaccines has been resurrected. Previous autologous, whole cell tumor vaccine trials have not produced convincing results due, in part, to poor patient selection and inactivation methods that are harsh on the cells. Such methods can inadvertently alter protein structure and antigenic profile in ways that make vaccine candidates ineffective in stimulating immune response to autochthonous tumor cells. We decided to investigate a novel method for inactivating tumor cells that uses UVA/UVB light and the benign chemical riboflavin (Riboflavin and UV Light Inactivation, RF+UV). This process is fast and results in complete inactivation of the tumor cells, but preserves tumor cell integrity and antigenicity due to its rapid, yet gentle inactivation process. Our results demonstrate that the inactivation is complete, that proteins are preserved on the surface of the tumor cells, and that the inactivated tumor cells are immunogenic in that they induce dendritic cell maturation, increased IFNγ production, and the generation of tumor cell-specific IgG immune responses. Moreover, when formulated with an adjuvant (“Innocell vaccine”) and tested in two different murine primary tumor models and one metastatic tumor model, the vaccine led to decreased tumor growth, prolonged survival and decreased metastatic disease. In addition, immune cells obtained from tumor tissue following vaccination showed a decrease in exhausted and regulatory cells, suggesting that activation of intratumoral T cells may be playing a role leading to the reduce tumor growth. Lastly, tumor tissue was obtained from 3 client-owned dogs with spontaneous tumors and used to generate an autologous Innocell vaccines. The vaccine was well-tolerated and induced an inflammatory response in 2 of the 3 dogs. This data suggests that the RF+UV process of inactivating tumor cells for use as antigen-presenting agents in cancer vaccine therapy may provide a more rapid, safer and gentler way to generate autologous whole tumor cell vaccines for use in cancer patients. Citation Format: Amanda Michele Guth, Raymond Goodrich, Haemin Park, Matthew Gladstone, Crystal Shanley, Lindsay Hartson, Jon Weston. A novel method for inactivating tumor cells for use in a personalized cancer vaccine [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4574.