Abstract CT036: Early trial results of an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in ovarian cancer patients
Authors: Peace Kaitlin M. , Vreeland Timothy J. , Clifton Guy T. , Hale Diane F. , Jackson Doreen O. , Berry John S. , Trappey Alfred F. , Herbert Garth S. , Hardin Mark O. , Nichol Pauline T. , Yin Sook L. , Yu Xianzhong , Wagner Thomas E. , Peoples George E. 
Published: July 2017

Abstract
Introduction: Late-stage ovarian cancer remains difficult to treat with 1-year disease free survival rates of roughly 55% and 40% in patients (pts) with stage III and IV disease, respectively1. To date, the majority of ovarian cancer vaccines have targeted specific tumor-associated antigens with little benefit. Our vaccine approach harnesses the most potent antigen presenting cell in the body, the dendritic cell (DC), and exposes these cells to the full repertoire of tumor antigens from an individual’s cancer. Autologous tumor lysate (TL) is loaded into yeast cell wall particles (YCWP) that are naturally and efficiently taken up into the pt’s DC ex vivo. This process uses a small amount of blood and tumor and can be completed in 48 hours. The autologous TL, particle-loaded, DC (TLPLDC) vaccine is then injected intradermally (ID). This vaccine is being tested in multiple tumor types, and here we present the results in ovarian cancer.
Methods: Pts with stage III or IV ovarian cancer were identified prior to surgical intervention for enrollment and tumor acquisition. Pts were treated with standard of care therapy, then enrolled in the per protocol (PP) phase I/IIa trial if disease-free or in an open label treatment registry (OTR) if they had measureable residual disease. A tumor sample (&gt;1mg) was collected at the time of surgery, and 120mL of blood (or 50mL after a single dose of Neupogen) was drawn to isolate the pt’s DC. TL was produced through freeze/thaw cycling and loaded into YCWP, which were introduced to DC for phagocytosis; thus creating an individualized TLPLDC vaccine for each pt. Each vaccine dose contained 1x106 TLPLDC, which was injected ID in the thigh. In the PP group, the primary vaccine series (PVS) consisted of monthly vaccination x3 followed by boosters at 6 and 12 months. In the OTR, the PVS consisted of monthly vaccination x4 followed by boosters every 3 months. Pts were monitored for toxicity and recurrence or progression of disease, respectively.
Results: A total of 15 pts have been treated to date, (PP: 8, OTR: 7 with 1 pt vaccinated on compassionate use). 100% of pts had successful creation of vaccine. Minimal toxicities (all ≤ grade 2) were reported. To date, in the OTR, 1 pt has shown a complete response, 1 has stable disease, and 4 have had progressive disease (PD; only 1 pt with PD completed the PVS). In the PP group, after a median follow up of 10.8 months, 3 pts (37%) have recurred (only 1 of these pts completed PVS), while 5 pts (63%) remain disease free.
Conclusions: We have shown that the TLPLDC vaccine can be made efficiently (requiring only a small amount of blood, tumor and time) and is safe and well-tolerated. Our results suggest that the vaccine is better suited for the adjuvant setting rather than pts with residual disease. This data provides justification for a larger clinical trial in stage III/IV ovarian cancer pts in the adjuvant setting.
1 Kurta M, et al. Prognosis and conditional disease-free survival among pts with ovarian cancer. J Clin Oncol. 2014;32(36):4102-12.
Citation Format: Kaitlin M. Peace, Timothy J. Vreeland, Guy T. Clifton, Diane F. Hale, Doreen O. Jackson, John S. Berry, Alfred F. Trappey, Garth S. Herbert, Mark O. Hardin, Pauline T. Nichol, Sook L. Yin, Xianzhong Yu, Thomas E. Wagner, George E. Peoples. Early trial results of an autologous tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine in ovarian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT036. doi:10.1158/1538-7445.AM2017-CT036