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Evaluating Immune Modulatory Therapeutic Strategies for Diffuse Intrinsic Pontine Glioma

Abstract Details

2020, MS, University of Cincinnati, Pharmacy: Pharmaceutical Sciences.
Diffuse intrinsic pontine glioma (DIPG) is a rare and lethal pediatric brain tumor arising in?the?midline structures of the brain, namely the pons and thalamus. Surgery is not an option for these patients, and, to date, no chemotherapy has significantly improved survival. While radiation therapy provides some benefit, the average survival remains dismal, with patients succumbing to disease within a year post diagnosis. Thus, there is a critical need to develop new therapeutic strategies to improve the outcome for patients and their families. One approach which has elicited a robust and durable response?in several solid and liquid cancers is immune checkpoint inhibition. Immune checkpoint inhibitors harness the immune system to promote tumor cell clearance and have been most beneficial in tumors which display immune cell infiltration prior to treatment.?Although many tumors, including DIPG, display limited immune cell infiltration, recent studies in other solid tumors have identified small molecule inhibitors that increase immune cell infiltration and activity. In this study, we evaluate the potential of using small molecule inhibitors to improve response to immune checkpoint inhibitor treatment?in a mouse model of DIPG. Analysis of selected small molecule inhibitors reveals differential sensitivity of mouse DIPG cell lines, nominating candidates which may increase immune cell infiltration and recognition of tumor cells. An?in vivo?study of a cyclin dependent kinase 4/6 inhibitor combined with immune checkpoint inhibitor demonstrates the feasibility of these types of studies in our mDIPG models and reveals increased immune cell recruitment related to immune check point inhibition.
Timothy Phoenix, Ph.D. (Committee Chair)
Rachid Drissi, Ph.D. (Committee Member)
Joan Garrett, Ph.D. (Committee Member)
64 p.

Recommended Citations

Citations

  • Furnish, R. (2020). Evaluating Immune Modulatory Therapeutic Strategies for Diffuse Intrinsic Pontine Glioma [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595849080346532

    APA Style (7th edition)

  • Furnish, Robin. Evaluating Immune Modulatory Therapeutic Strategies for Diffuse Intrinsic Pontine Glioma. 2020. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595849080346532.

    MLA Style (8th edition)

  • Furnish, Robin. "Evaluating Immune Modulatory Therapeutic Strategies for Diffuse Intrinsic Pontine Glioma." Master's thesis, University of Cincinnati, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1595849080346532

    Chicago Manual of Style (17th edition)