Abstract B92: The tubulin-targeting agent BNC105 potentiates the efficacy of immune checkpoint inhibitors in preclinical models of colorectal cancer

• Published in: Molecular cancer therapeutics 2015-12, Vol.14 (12_Supplement_2), p.B92-B92
• Main Authors: Lavranos, Tina C., Beaumont, Donna, Inglis, Daniel, Scherer, Michaela, Hawkins, Chloe, Leske, Annabell F., Kremmidiotis, Gabriel
• Format: Article
• Language: English
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.TARG-15-B92

BNC105 is a tubulin depolymerisation agent. Its activity includes effects on both cancer cells and on solid tumor microvasculature. BNC105 shows evidence of strong anti-cancer efficacy in vitro and in animal models. In solid tumors its efficacy is driven by selective destruction of tumor vasculature (Vascular Disrupting Agent - VDA) and direct action on tumor cells through suppression of their proliferation. In non-proliferating blood cancers (e.g. Chronic Lymphocytic Leukaemia) BNC105 activates pro-apoptotic proteins, which mediate cancer cell death. BNC105P may be useful in the treatment of human cancers both as a monotherapy and also in combination therapies. Two separate in vivo studies were conducted to assess the potential therapeutic utility of combining BNC105 with antibodies that target PD-1 or CTLA4. The in vivo models utilised were xenografts of the murine colorectal cancer cell lines MC38 and CT26. C57/BL6 mice were inoculated subcutaneously with MC38 cells and treatment commenced when tumors reached a volume of approximately 100-150mm3. BNC105 was administered at 10 mg/kg i.v. on Day 1, 8 and 15 andanti-PD-1 antibody (Clone RMP1-14) was administered at 3.5mg/kg i.p. on Day 1, 4, 8, 12 and 16. Tumor growth inhibition was evident as early as Day 8 of the treatment period especially in the combination group compared to control group (p