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Grant Aims to Deliver First Stem-Cell Immunotherapy in Ovarian Cancer

Christin Melton
Published: Monday, Jan 19, 2015

Dr Alexandria Phan

Kunle Odunsi, MD, PhD

The New York State Stem Cell Science Program (NYSTEM) recently awarded a 4-year $11.9 million grant to Roswell Park Cancer Institute (RPCI) in Buffalo, New York, to fund research and development of a stem-cell based treatment for ovarian cancer. Kunle Odunsi, MD, PhD, FRCOG, FACOG, executive director of RPCI’s Center for Immunotherapy, and his team are pioneers in immunotherapy research for ovarian cancer, and he spoke with Targeted Oncology about how the grant will contribute to their efforts. He also explained their progress in reengineering adult hematopoietic stem cells (HSCs) to fight ovarian cancer and the possibilities of adoptive T-cell therapy.

The American Cancer Society estimates that in 2015, more than 21,000 women will receive an ovarian cancer diagnosis and approximately 14,000 women will die of the disease.1 Ovarian cancer is aggressive, and many women have advanced disease at diagnosis.2 Approximately 85% of those who achieve remission will relapse, and median survival for patients with relapse is 12 to 24 months.2 A great need exists for new therapies, particularly for women with epithelial ovarian cancer whose disease is platinum-resistant or who relapse after treatment with a platinum-based regimen. Odunsi and his colleagues at RPCI are hopeful that the stem-cell based immunotherapy they are developing for epithelial ovarian cancer will someday help improve these dire statistics.

OncLive: How long have you been focused on ovarian cancer research, and what lies behind your efforts?

Odunsi: For more than 10 years now, our team has been studying, in preclinical and clinical settings, several different approaches for delivering immune therapies for ovarian cancer, and we’ve made several important discoveries that we’re applying in our current projects. The desperate need for better, longer-lasting therapies to offer women with ovarian cancer has always been the driving factor behind this work.

How will the NYSTEM grant further those efforts?

The NYSTEM grant will support the first clinical trial to utilize adult HSCs in cancer immunotherapy. It is tremendously important support that allows us to leverage other resources and fast-track our efforts to get these therapies to patients.

Is your stem cell approach the first immunotherapy being studied for ovarian cancer?

This is the first study, to our knowledge, that will directly examine the potential of reprograming adult HSCs into cancer-fighting immune cells able to provide long-term control of tumor growth. Previous studies by us and others have utilized mature immune cells in adoptive cellular therapy of cancers. Our pioneering NY-ESO-1 vaccine studies were the first studies to harness the potential of the patient’s own immune system to mount a response against their ovarian cancer cells.

There are many types of immunotherapy, including but not limited to immunomodulatory agents, monoclonal antibody therapy, vaccines, and cellular therapy. Each of these therapeutic strategies is tailored for the patient depending on the type and stage of his or her disease.

What have your studies shown so far with this approach?

We have a lot of data on the ability of the immune system to recognize and control ovarian cancer. Data from our preclinical studies using stem cells are not yet published, but we have demonstrated that adult HSCs can be programed to mature into functional antitumor immune cells and that these mature cells persist for a long period, thereby resulting in improved tumor control.

How are the adult HSCs obtained?

Along with mature T cells, adult HSCs are present in blood and are drawn from patients through standard leukapheresis. Based on the expression profile of unique cell surface markers, HSCs are isolated from the blood and can be further engineered to become T cells that have the potential to recognize tumor cells and attack them. Patients receive their own reengineered stem cells.

How do you reprogram the stem cells to identify and eliminate ovarian cancer cells?

Our work has focused on a unique class of tumor antigens known as cancer testis antigens. These are proteins primarily overexpressed on tumor cells and in the adult male testes but not in other normal tissues. This antigen, NY-ESO-1, can be targeted for immune-mediated destruction without causing unwanted damage to normal healthy tissue.

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