Abstract 2764: In vivo mouse model data demonstrating reduction in tumor cell proliferation following intratumoral administration of TYME 18

Introduction: TYME-18 is a combination of an ambiphilic steroid acid, tauroursodeoxycholic acid (TUDCA) and surfactants (N-methyl pyrrolidone, polidocanol, and linoleic acid) administered intratumorally to induce regression without injuring adjacent tissue. Methods: Balb/C mice were inoculated with CT-26 cancer (106 cells) until a tumor was established to approximately 100 mm3. An initial feasibility semi-quantitative assessment was performed with 10 animals (table 1). A larger confirmatory experiment testing the individual components of TYME-18 was also conducted (tables 2 & 3). Mice received intra-tumoral injections of TYME-18 with surfactants; or surfactants without TUDCA, or vehicle with measurements 3 times/wk. Intra-tumoral injections were administered 6 times at 3-day intervals over a total of 4 weeks. Animals were sacrificed when tumors reached 2000 mm3 or at the end of the study (16 weeks). Results: TYME-18 demonstrated a significant difference between treated and untreated animals (see Tables 1, 2, 3). A minor reduction in tumor cell mass was observed in response to the surfactant, with the greatest response (ANOVA p=.001) observed in the TYME-18 (surfactant + TUDCA) (table 2). Discussion: The local administration of an ambiphilic steroid acid along with surfactants, impeded the ability of tumors to increase in size. Both the surfactants and the ambiphilc steroid acid contributed to this effect with an apparent synergistic effect. Aside from the physical chemical acid effect on tissue, ambiphilic steroid acids are now recognized as important regulators of energy metabolism. Their effects on FXR, LXR, PPAR-α, PPAR-γ are known to regulate important changes in energy metabolism including insulin utilization, the sensitivity of the insulin receptor, the transcription of the genes that mediate glucose and lipid metabolism as well as various immune effects; all of which could be useful in the treatment of cancer. Currently, TYME-18 is under investigation as a simple and nontoxic treatment for tumors for which systemic therapy is not indicated. Citation Format: John Rothman, Steve Hoffman, Allyson Ocean, Jonathan Eckard, Giuseppe Del Priore, Martin Fernandez-Zapico. In vivo mouse model data demonstrating reduction in tumor cell proliferation following intratumoral administration of TYME 18 [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 2764.