NYSTEM-funded clinical trial reprograms both blood stem cells and T cells as treatment of patients with ovarian cancer
- New approach studied in patients with some incurable gynecologic cancers
- Patients receive their own cells, re-engineered to target, kill cancer cells
- First team to modify stem cells and mature T cells to treat ovarian cancer
BUFFALO, N.Y. — A clinical trial underway at Roswell Park Comprehensive Cancer Center will assess a brand-new immunotherapy approach in patients with cancer of the ovaries, fallopian tubes or peritoneum that has recurred despite earlier treatment. Enabled by a major grant from New York Stem Cell Science, or NYSTEM, the study takes the new approach of reprogramming a patient’s own blood stem cells, or hematopoietic stem cells, to serve as a “living drug” that can generate a lasting supply of two key types of immune cells: CD4+ and CD8+ T cells.
Led by Kunle Odunsi, MD, PhD, FRCOG, FACOG, Deputy Director of the Buffalo-based cancer center and Executive Director of its Center for Immunotherapy, the study is the centerpiece of an $11.9 million competitive grant awarded by NYSTEM in 2015. One patient has received treatment as part of this early-phase clinical trial, which will initially be available only at Roswell Park and is expected to enroll 15 patients.
“With state support under Governor Cuomo, scientists in New York are attempting and accomplishing things unheard of outside science fiction just a few years ago,” says Dr. Howard Zucker, Commissioner of the New York State Department of Health, which administers the NYSTEM initiative. “I applaud the groundbreaking work being done at Roswell Park, to expand the definition of healthcare by using cancer patients’ own genetically re-engineered cells to create treatments specially designed for them.”
A unique element that distinguishes this new strategy from any other existing cancer treatment is the novel approach of genetically engineering a patient’s own hematopoietic stem cells and mature T cells with tumor-recognizing T-cell receptors. Once infused into patients, these “designer cells” generate two different types of immune cells — CD8+ T cells to kill tumor cells, and CD4+ “helper” T cells to give the CD8+ T cells a needed boost. The path to this new strategy for adoptive cell therapy (ACT), or T-cell transfer therapy, says Dr. Odunsi, began with the realization that the inability of infused T cells to persist for a long time represents a key stumbling block in ACT.
“A major gap in the field has been the question of how to provide a long-term supply of antitumor T cells,” says Dr. Odunsi, who is also Chair of Gynecologic Oncology and M. Steven Piver Professor of Gynecologic Oncology at the Buffalo-based cancer center. “Working on this problem for many years, our team at Roswell Park identified and isolated unique T-cell receptors (TCRs) from CD8+ T cells that have robust ability to recognize cancer cells. We also isolated TCRs from CD4+ cells that not only help the CD8+ T cells to be stronger, but have the unique ability to directly recognize and kill cancer by themselves. The entire platform combines genetic engineering of hematopoietic stem cells and mature T cells with these unique TCRs, leading to tumor attack from three or four different directions.”
Patients on the study will receive two intravenous infusions a few days apart from one another — first hematopoietic stem cells drawn from their own blood but re-engineered with one of the tumor-recognizing receptors. Once infused into patients, the re-engineered hematopoietic stem cells will develop into mature T cells capable of destroying tumor cells that express a particular protein, NY-ESO-1 — an antigen primarily found only in cancer cells. The second infusion will consist of their own T cells, genetically modified with another unique TCR. Together, both cell types are expected to provide more durable antitumor responses than infusion of either cell type alone — and potentially prevent the cancers from recurring.
This strategy, which originated out of Roswell Park, has never before been tested in humans. Preclinical studies by Dr. Odunsi and his team at the Center for Immunotherapy, which includes Richard Koya, MD, PhD, Thinle Chodon, MD, PhD, Junko Matsuzaki, PhD, and Takemasa Tsuji, PhD, suggest that this approach has the potential to be effective in many solid-tumor cancers — including ovarian cancer, fallopian-tube cancer and primary peritoneal cancers.
“We expect that these approaches will complement one another well, uniting the stem cells’ long life span and capacity for self-renewal with the ability of our receptor-driven method of instructing immune cells to recognize and destroy cancer cells,” notes Dr. Koya, who is Associate Director of Roswell Park’s Center for Immunotherapy and one of the architects of this approach. “To the best of our knowledge, reprogramming hematopoietic stem cells for adoptive T-cell immunotherapy to generate a long-lasting supply of antitumor CD4-TCR T cells is completely novel.”
Drs. Odunsi and Koya are co-founders of Tactiva Therapeutics Inc., a Roswell Park biotech spinoff company that has licensed these technologies in order to expand the platform for further application and commercial development.
Currently, no curative treatments exist for chemotherapy-resistant advanced ovarian, fallopian-tube and peritoneal cancers.
The NYSTEM clinical trial is the latest cellular therapy available through Roswell Park’s Transplant & Cellular Therapy Center, where a specially trained team oversees the care of patients receiving both FDA-approved CAR-T therapies and investigational cell therapy approaches being studied as part of clinical trials.
Roswell Park Comprehensive Cancer Center is a community united by the drive to eliminate cancer’s grip on humanity by unlocking its secrets through personalized approaches and unleashing the healing power of hope. Founded by Dr. Roswell Park in 1898, it is the only National Cancer Institute-designated comprehensive cancer center in Upstate New York. Learn more at www.roswellpark.org, or contact us at 1-800-ROSWELL (1-800-767-9355) or ASKRoswell@RoswellPark.org.
Annie Deck-Miller, Senior Media Relations Manager