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2024 Recipient — Bethany Hannafon, PhD

Photo: Dr. Bethany Hannafon smiling in professional headshot, wearing white lab coat

Bethany Hannafon, PhD

Development of a novel DCLK1-targeted CAR-T to prevent ovarian cancer metastatic recurrence

Project Summary

Ovarian cancer (OvCa) is characterized by disease recurrences due to the persistence of drug-resistant cancer cells known as cancer stem cells (CSCs). CSCs retain the ability to self-renew, propagate new tumors, and drive resistance to chemotherapy. Doublecortin-like kinase 1 (DCLK1) is a CSC-related protein and a regulator of programs that drive tumor metastasis and drug resistance. We show that in OvCa, DCLK1 is associated with poor survival, is highly expressed in chemo-resistant compared to sensitive cells, and that inhibition of DCLK1 enhances sensitivity to chemotherapy. Chimeric antigen receptor T (CAR-T) is a type of immunotherapy whereby a patient’s T cells are engineered to attack specific tumor surface antigens. DCLK1 is expressed at the cell surface and is increased on the surface of ovarian cancer cells, thus providing a novel tumor antigen. We hypothesize that engagement of CSCs that express DCLK1, with a novel CAR-T, will overcome chemoresistance, reduce tumor growth, and metastasis, and prevent recurrence. In this study, we will systematically design, optimize, and investigate a DCLK1-targeted CAR-T therapy. At completion, we will have identified a CAR-T with superior efficacy and persistence for the treatment of metastatic chemo-resistant OvCa that will ultimately provide safe and effective repression of recurrent metastases without the massive comorbidities associated with prolonged traditional chemotherapy, which will fulfill a major unmet medical need.

Bio

Bethany Hannafon, Ph.D. is an Assistant Professor of Gynecologic Oncology at the Stephenson Cancer Center, University of Oklahoma Health Sciences Center (OUHSC). Dr. Hannafon earned a dual Ph. D. in the Program in Molecular Medicine and Cell and Molecular Biology from Boston University School of Medicine and completed postdoctoral training in cancer biology/pathology at Dana-Farber Cancer Institute and OUHSC.

Dr. Hannafons’ research aims to understand the cellular and molecular mechanisms that drive ovarian cancer development, progression, and therapeutic resistance and to discover novel treatment strategies to overcome resistance, prevent recurrences, and improve patient outcomes. Her recent efforts have focused on evaluating the role of doublecortin-like-kinase 1 (DCLK1) in promoting platinum resistance and cancer-stem-cell phenotypes in ovarian cancer. Novel treatment strategies, such as targeting DCLK1, that can overcome platinum resistance are urgently needed to reduce chemotherapy resistance and positively impact ovarian cancer patient outcomes.