The Goldilocks Window of Personalized Chemotherapy: An Immune Perspective

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 patient's 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.

Model-Based Inference and Classification of Immunologic Control Mechanisms from TKI Cessation and Dose Reduction in Patients with CML

“…For class C patients with a weak immune response, our model predicts that TFR achievement depends on an optimal balance between leukemia abundance and immunologic activation before treatment cessation and could be accomplished by a narrowly adapted TKI administration. These results are in line with those from a recent modeling study that suggested the existence a "Goldilocks Window" in which treatment is required to optimize the balance between maximal tumor reduction and preservation of patient immune function (26).…”

“…Mathematical oncology has been established as a complementary effort to obtain insights into cancer biology and treatment. At the same time, model-based understanding of individual patient records is developing into a key method for devising adaptive therapies in the coming era of personalized medicine (23)(24)(25)(26). CML is a show-case example, where several models have propelled the conceptual understanding of CML treatment dynamics (5-7, 9, 27-33) and are considered for the design of new clinical trials (34).…”