Abstract 2845: Synthetic fusion cytokine, GIFT4, transduced autologous peritoneal immune cells - a novel cell therapy for the treatment of ovarian cancer
Authors: Sharma Sejal Tarun , Paul Pradyut , Das Rahul , Yuan Shala , Barroilhet Lisa , Vazquez Jessica , Stanic Aleksandar K. , Galipeau Jacques , Patankar Manish 
Published: June 2022

Ovarian Cancer is the 5th leading cause of mortality among women. Even with the development of modern chemo and biologic therapies, there has not been a significant increase in the progression-free and overall survival of patients with high grade serous ovarian tumors. The goal of this study is to develop an individualized cell therapy approach for immunologic targeting of this cancer. Our proposed approach is based on harvesting and subsequently arming natural immune cells present in the peritoneal fluid (ascitic fluid) that accumulates in most ovarian cancer patients and is removed by paracentesis and discarded to alleviate discomfort. Using multiparameter flow cytometry with three 16-18 component antibody panels we have carefully characterized the T cells, dendritic cells and innate lymphoid cells present in the peritoneal fluid of 15 ovarian cancer patients. Analysis of the data using tSNE identified multiple clusters of immune cell subsets. These data indicated that in each patient, a substantial percentage of adaptive and innate lymphoid cells are present that under appropriate conditions can be reactivated to recognize and target autologous tumors (Vazquez, Jessica, et al. "Identification of unique clusters of T, dendritic, and innate lymphoid cells in the peritoneal fluid of ovarian cancer patients." American Journal of Reproductive Immunology 84.3 (2020): e13284). Our goal now is to use fusokines, chimeras of two distinct cytokines, to weaponized the ascitic immune cells and employ them as autologous cell therapy against ovarian cancer. The first candidate under investigation is GIFT4, a fusokine composed of GM-CSF and IL-4 that has previously been shown to eradicate Melanoma in mouse model. Using Vector Builder, we designed and produced lentiviral vectors to express GIFT4 in primary immune cells. The efficiency of human GIFT4 expression in primary immune cells was optimized by testing different promoter constructs. The efficiency of transduction was determined by monitoring the primary immune cells for secretion of GIFT4 using IL-4 and GM-CSF ELISA. The effect of GIFT4 expression on the phenotype of the primary immune cells is under investigation using multiparameter flow cytometry. The tumor targeting potential of the GIFT4 transduced peritoneal immune cells is being investigated in an ID8 mouse model of ovarian cancer. Effects of GIFT4 on the activation of specific subtypes of ascetic immunocytes and their in vivo effects in neutralizing ID8 cells in immunocompetent C57BL/6 mice will be instrumental for developing a novel fusokine-based individualized immune cell therapy for ovarian cancer.

Citation Format: Sejal Tarun Sharma, Pradyut Paul, Rahul Das, Shala Yuan, Lisa Barroilhet, Jessica Vazquez, Aleksandar K. Stanic, Jacques Galipeau, Manish Patankar. Synthetic fusion cytokine, GIFT4, transduced autologous peritoneal immune cells - a novel cell therapy for the treatment of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2845.