Abstract 3188: Transimmunization prevents recurrence and reprograms the immune milieu in a mouse model of ovarian cancer
Authors: Alvero Ayesha B. , Hanlon Douglas , Pitruzzello Mary , Filler Renata , Robinson Eve , Sobolev Olga , Tedja Roslyn , Ventura Alessandra , Edelson Richard L. , Mor Gil 
Published: August 2019

Introduction: Targeting recurrent disease is vital in the improvement of survival in ovarian cancer patients. Transimmunization (TI) is a modification of extracorporeal photochemotherapy, which is a dendritic cell (DC)-based vaccination, currently used in cutaneous T cell lymphoma but has never been tested in gynecologic tumors. The objective of this study is to determine if TI can induce a tumor-specific immune response capable of preventing recurrence in ovarian cancer.

Methods of study: Ovarian cancer cells expressing mCherry fluorescent protein were injected i.p. in C57bl/6 mice to mimic the establishment of recurrent disease. These cells (TKO cancer cells) were isolated from spontaneously formed ovarian tumors from p53LSL-R172H/+Dicerflox/floxPtenflox/flox Amhr2cre/+ mice. Tumor burden was quantified using mCherry fluorescence ROI area. TI vaccination was conducted as follows: (1) cancer cells were treated with 8-MOP and exposed to UVA to induce apoptosis; (2) PBMCs were collected from tumor-bearing mice, mixed with apoptotic cancer cells, and circulated through the TI chamber to induce functional DC from monocytes; (3) cells collected were incubated overnight to facilitate antigen uptake and presentation and injected i.p. Treatment groups were as follows: (1) PBS control, n = 20 ; (2) TI TKO, n =10 (i.e. using apoptotic TKO cells); and (3) TI YUMM, n = 10 (using apoptotic mouse melanoma YUMM1.7 cells as antigen-unrelated control). Immune milieu was characterized by IHC on tumors and FACS analysis using cells isolated from peritoneal lavage.

Results: Eighty percent of mice in the TI TKO group were disease free compared to 35% in the PBS control group and 40% in the TI YUMM group. In addition, TI TKO vaccination (p &lt; 0.0001), but not TI YUMM vaccination (p = 0.1079) induced a statistically significant decrease in tumor kinetics compared to PBS control. IHC analysis showed significantly higher levels of infiltrating CD8+ (p = 0.0037) and CD4+ T cells (p = 0.0079) in TI TKO group compared to PBS group. Similarly, mice in the TI TKO group have higher i.p. levels of CD8+/CD44+/CD62L+ central memory T cells (p = 0.004), higher levels of CD8+/CD44+/CD62L- effector memory T cells (p = 0.03), lower levels of CD8+/CD44-/CD62L+ naïve T cells (p = 0.02), and lower levels of CD11b+/Gr-1high myeloid-derived suppressor cells (p = 0.01) compared to PBS control group. Levels of these cells in TI YUMM group were not significantly different from the PBS control.

Conclusion: We demonstrate for the first time that TI vaccination with autologous cancer cells can prevent recurrence and modify the immune phenotype in ovarian cancer. TI efficacy depends on the tumor antigen source, confirming TI as an antigen-specific DC-based immunotherapy. Our results highlight the value of TI in ovarian cancer and its potential application to other i.p. cancers.

Citation Format: Ayesha B. Alvero, Douglas Hanlon, Mary Pitruzzello, Renata Filler, Eve Robinson, Olga Sobolev, Roslyn Tedja, Alessandra Ventura, Richard L. Edelson, Gil Mor. Transimmunization prevents recurrence and reprograms the immune milieu in a mouse model of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3188.