The Goldilocks Window of Personalized Chemotherapy: An Immune Perspective

Park, D. S.; Robertson-Tessi, M.; Maini, P.; Bonsall, M. B.; Gatenby, R. A.; Anderson, A. R.

doi:10.1101/495184

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bioRxiv · 10.1101/495184

The Goldilocks Window of Personalized Chemotherapy: An Immune Perspective

Park, D. S.·Robertson-Tessi, M.·Maini, P.·Bonsall, M. B.·Gatenby, R. A.·Anderson, A. R.

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Abstract

The immune system is increasingly being recognized for its untapped potential in being recruited to attack tumors in cancer therapy. The main challenge, however, is that most tumors exist in a state of immune tolerance where the patients immune system has become insensitive to the cancer cells. In order to investigate the ability to use chemotherapy to break immune tolerance, we created a mathematical modeling framework for tumor-immune dynamics. Our results suggest that optimal chemotherapy scheduling must balance two opposing objectives: maximal tumor reduction and preserving patient immune function. Successful treatment requires therapy to operate in a Goldilocks Window where patient immune health is not overly compromised. By keeping therapy just right, we show that the synergistic effects of immune activation and chemotherapy can maximize tumor reduction and control.\n\nStatement of SignificanceIn order to maximize the synergy between chemotherapy and anti-tumor immune response, lymphodepleting therapy must be balanced in a Goldilocks Window of optimal dosing.

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Park, D. S., Robertson-Tessi, M., Maini, P., Bonsall, M. B., Gatenby, R. A., Anderson, A. R.. 2018-12-13. The Goldilocks Window of Personalized Chemotherapy: An Immune Perspective. https://doi.org/10.1101/495184

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