P11.03.B BXQ-350: Modulating ceramide and Sphingosine-1-Phosphate for anti-tumor activity and potential mitigation of chemotherapy induced peripheral neuropathy
Year: 2022
Type: conference-abstract
Abstract: Background Sphingolipids are a class of bioactive signaling molecules implicated in multiple cellular processes and molecular pathways. Many publications have indicated that among these sphingolipids, sphingosine-1-phosphate (S1P) is a key sphingolipid that promotes cancer cell survival and proliferation, activates multiple oncogenic pathways, and stimulates immuno-suppressor cell populations promoting a pro-tumoral microenvironment. Many of these publications have also implicated S1P with chemotherapy induced peripheral neuropathy, a debilitating and serious side effect that may impact therapeutic treatments and patient’s quality of life. Material and Methods BXQ-350 is a nanovesicle of Saposin C, an allosteric activator of sphingolipid metabolism, that has broad anticancer activity, potentially in part by lowering systemic S1P levels. BXQ-350 was investigated in a Phase 1 dose-escalation safety study in an all-comer cancer patients with advanced solid malignancies, including CNS tumors (NCT02859857) to determine its safety profile and its potential clinical activity as a single agent in cancer patients. Samples were collected to determine pharmacokinetics and explore potential biomarkers. Results 11 patients (~15% of evaluable patients) with advanced disease had a clinical benefit and amongst these, 8 patients (~11% of evaluable patients) had PFS> 6 months with 2 patients still on study five years after enrollment. Analysis of patient’s samples revealed that BXQ-350 decreases systemic S1P levels in the majority of the patients experiencing a clinical benefit. In addition, several patients with established CIPN spontaneously reported improvements of their symptoms shortly after BXQ-350 administration. Analysis of these patients’ samples also revealed that S1P systemic levels had decreased, as well as pro-inflammatory cytokines associated with CIPN. Conclusion While these results are exploratory and preliminary in nature, they suggest that BXQ-350’s mechanism of action may represent a novel anti-cancer approach that may also mitigate CIPN.
Source: Neuro-Oncology
Authors: G H Tapolsky, J C Morris, E Yilmaz, J L Villano, C Muller, R C Curry, III, V K Puduvally, T M Wise-Draper, R Takigiku, R Wesolowski
Institutions: Bexion Pharmaceuticals (United States), University of Cincinnati, University of Cincinnati Medical Center, Cleveland Clinic, University of Kentucky, UNM Comprehensive Cancer Center, University of Houston, The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W4294679067