Novel Formulation of Cannabinoid Analogues Used in Cancer Therapy.

e19536 Background: Diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) represent the most common and most aggressive forms of Non-Hodgkin lymphoma (NHL) respectively. Previous work has demonstrated CB1 antagonists as potential therapeutics for both DLBCL and MCL. Our drug formulation VYR-206 was developed from existing obesity treatment Rimonabant, a CB1 antagonist, by the addition of our tetraazacyclic (N4) conjugate derivative. The addition of N4 allows the potential for image guided theranostic application for diagnosis, precision and assessment of therapeutic response through radiotracer chelation. Our study is aimed at demonstrating the viability of our novel conjugate formulation VYR-206 and comparing it with its parent analogue Rimonabant in DLBCL and MCL cell lines for sensitivity or resistance. Methods: Cells from representative DLBCL and MCL cell lines were plated at 5,000 cells per well. The cells were incubated for 72 hours in 20 µL medium with 10% FBS and varied concentrations of experimental cannabinoid antagonist VYR-206, Rimonabant, or dimethylsulfoxide (DMSO) vehicle. Viability assays were conducted using Celltiter-Glo Luminescent Cell Viability Assay. Experiments were performed 2-3 times independently with each concentration tested in triplicate. Results: Drug effectiveness of compound VYR-206 was compared to CB1 antagonist Rimonabant with N4 as a control in both DLBCL and MCL cell lines. Drug VYR-206 follows closely to Rimonabant in VYR-206 sensitive DLBCL cell lines with reduction of viability at concentrations < 100μM and 0% of control at 200μM. In VYR-206 resistant DLBCL cell lines reduction of viability occurs at concentration of 100μM or more, still with 0% of control occurring at 200μM. Drug VYR-206 appears to show more effectiveness in VYR-206 sensitive MCL cell lines, showing a reduction in viability at concentrations < 50μM with 0% of control at 100μM. In VYR-206 resistant MCL cell line Rec-1, drug VYR-206 fails to decrease viability below 50% of control even at concentrations of 400μM. Conclusions: VYR-206 has the potential for both the treatment and assessment of the efficacy of cannabinoid therapy in malignant lymphoma cancer.