An in silico exploration of combining Interleukin-12 with Oxaliplatin to treat liver-metastatic colorectal cancer

Background Combining anti-cancer therapies with orthogonal modes of action, such as direct cytotoxicity and immunostimulatory, hold promise for expanding clinical benefit to patients with metastatic disease. For instance, a chemotherapy agent Oxaliplatin (OXP) in combination with Interleukin-12 (IL-12) can eliminate pre-existing liver metastatic colorectal cancer and protect from relapse in a murine model. However, the underlying dynamics associated with the targeted biology and the combinatorial space consisting of possible dosage and timing of each therapy present challenges for optimizing treatment regimens. To address some of these challenges, we developed a predictive simulation platform for optimizing dose and timing of the combination therapy involving Mifepristone-induced IL-12 and chemotherapy agent OXP.