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The Penn Ovarian Cancer Research Center
Clinical Research
One of OCRC’s goals is the establishment of a worldwide pioneer clinical research program for ovarian cancer therapy. We aspire to improve patients’ clinical responses and reduce toxicity from current chemotherapies by developing new immune therapy, gene therapy and combination therapy approaches.
To date, Christina Chu, MD has completed University of Pennsylvania Cancer Center (UPCC) protocol 01803, the first consolidation dendritic cell vaccine trial in ovarian cancer, where patients completing chemotherapy have received autologous dendritic cells loaded with tumor antigen HER2 and hTERT peptides plus cyclophosphamide. Currently we have UPCC-11807 open, a new whole-tumor antigen vaccine using tumor lysate-pulsed autologous dendritic cells in combination with bevacizumab and oral metronomic cyclophosphamide. This is an entirely autologous patient-tailored immune therapy strategy. This combination immunotherapy concept has been a direct development of studies conducted in the OCRC labs over the past 3 yrs and is partially sponsored by Northwest Biotherapeutics. Patients completing UPCC-11807 can enroll in protocol UPCC-01808, a phase I/II study that will test the feasibility, safety and clinical efficacy of adoptive transfer of vaccine-primed ex vivo CD3/CD28-costimulated peripheral blood lymphocytes following lymphodepletion with high dose cyclophosphamide and fludarabine, combined with vaccine boosts and oral metronomic cyclophosphamide.
Additional innovative studies include combination chemo-immunotherapy clinical studies where conventional chemotherapy is given together with recombinant interleukin-18 therapy, interleukin-12 gene therapy or CD137 antibody therapy.
Currently in development is a is a gene therapy trial in collaboration with BioCancell. This trial uses a DTA-H19 doubled stranded DNA plasmid carrying the gene for the DT-A chain under the regulation of H19 promoter sequence. DT-A chain expression is only triggered by the presence of H19 transcription factors that are upregulated in tumor cells. The selective initiation of toxin expression results in selective tumor cell destruction via inhibition of protein synthesis in the tumor cell, enabling highly targeted cancer treatment. This therapy will be paired with tumor tissue/cell screening for H19RNA expression that will be a prerequisite to therapy, in order to select the appropriate patient population to ensure patient-tailored targeted treatment.
We plan to launch additional clinical protocols stemming directly from the work in the lab. For example, we propose a Phase I trial of adoptive therapy using tumor infiltrating lymphocytes (TILs). The proposed trial will test the feasibility and safety of expanding TILs from ovarian tumors rescued surgically and administering them at completion of conventional carboplatin/paclitaxel chemotherapy using a simple dose-escalation design following lymphodepletion with high dose cyclophosphamide. In addition, we have generated a number of tools and combinatorial approaches targeting the tumor microenvironment that need to be tested urgently in the clinic. We expect that within the next 2 to 3 years, we will bring to the clinic one or more of these concepts. Additionally, an active research development program is optimizing lymphocyte engineering (see below) and we will bring to the clinic the first clinical study with autologous lymphocytes genetically engineered to kill ovarian cancer cells expressing mesothelin, developed in the laboratory of Carl H. June, MD. In summary, we are in the unique position to bring to the clinic innovative tools and combinatorial approaches for cancer immunotherapy.
The Division of Gynecologic Oncology also testing the latest in chemotherapy and targeted molecular therapy for ovarian cancer. Penn Gynecologic Oncology is a member of the Phase I/II program of the Gynecologic Oncology Group, a national organization running clinical trials in ovarian cancer. The Ovarian Cancer Research Center tests new chemotherapy drugs compounds with promising activity in ovarian cancer.
Active Clinical Trials
For a complete listing of all active clinical trials, please visit: http://www.uphs.upenn.edu/obgyn/research/trials.htm
Clinical Faculty
- George Coukos, MD, PhD - Director
- Sarah F. Adams, MD
- Christina Chu, MD
- Stephen C. Rubin, MD
- Lana Kandalaft, PharmD, PhD
Collaborators
- Josep Dalmau, MD, PhD
- Susan M. Domchek, MD
- Peter J. O'Dwyer, MD
- Bruce Levine, PhD
- Lilie Lin, MD
- Virginia A. LiVolsi, MD
- Cynthia M. McGrath, MD
- Kathy Montone, MD
- Thomas C. Randall, MD
- Donald L. Siegel, MD, PhD
- Evan S. Siegelman, MD
- Edward A. Stadtmauer, MD
- Daniel Sterman, MD
- Drew A. Torigian, MD
- Dan Vogl, MD
Support Team
- Maureen Bonnell, RN
- Cathi Ybarra, RN, BSN
- Nancy Gilinger, RN
- Phylis, Croshaw, LPN
- Patricia Murphy, LPN
- Simone J. Kutler
- Marcella Rominiecki-Sananta, RN
- Melissa Rivera, RN
