Ibrahim Chamseddine, Manoj Kambara, Priya Bhatt, Shari Pilon-Thomas, Katarzyna A Rejniak
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Optimizing the Efficacy of Vaccine-Induced Immunotherapy in Melanomas.
Cancer therapeutic vaccines are used to strengthen a patient's own immune system by amplifying existing immune responses. Intralesional administration of the bacteria-based emm55 vaccine together with the PD1 checkpoint inhibitor produced a strong anti-tumor effect against the B16 melanoma murine model. However, it is not trivial to design an optimal order and frequency of injections for combination therapies. Here, we developed a coupled ordinary differential equations model calibrated to experimental data and used the mesh adaptive direct search method to optimize the treatment protocols of the emm55 vaccine and anti-PD1 combined therapy. This method determined that early consecutive vaccine injections combined with distributed anti-PD1 injections of decreasing separation time yielded the best tumor size reduction. The optimized protocols led to a twofold decrease in tumor area for the vaccine-alone treatment, and a fourfold decrease for the combined therapy. Our results reveal the tumor subpopulation dynamics in the optimal treatment condition, defining the path for efficacious treatment design. Similar computational frameworks can be applied to other tumors and other combination therapies to generate experimentally testable hypotheses in a fairly unrestricted and inexpensive setting.
期刊介绍:
The Bulletin of Mathematical Biology, the official journal of the Society for Mathematical Biology, disseminates original research findings and other information relevant to the interface of biology and the mathematical sciences. Contributions should have relevance to both fields. In order to accommodate the broad scope of new developments, the journal accepts a variety of contributions, including:
Original research articles focused on new biological insights gained with the help of tools from the mathematical sciences or new mathematical tools and methods with demonstrated applicability to biological investigations
Research in mathematical biology education
Reviews
Commentaries
Perspectives, and contributions that discuss issues important to the profession
All contributions are peer-reviewed.