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A research team from Gates Institute at University of Colorado Anschutz has been awarded $1 million from Blood Cancer United® (formerly known as The Leukemia & Lymphoma Society) to advance a new immunotherapy approach for patients with treatment-resistant acute myeloid leukemia (AML).
The project, “A Phase 1 Study of Anti-CD64 CAR T Cells in Patients with Venetoclax-refractory Myeloid Neoplasms,” is a novel strategy targeting a specific protein found on leukemia cells that have become resistant to standard therapies. The Blood Cancer United Academic Clinical Trials grant will be used to support first-in-human trials of a chimeric antigen receptor (CAR) T cell, fully developed by CU Anschutz researchers for oncology research.
The phase 1 clinical trial and scientific analyses will be led by Mathew Angelos, MD, PhD, assistant professor of Medicine-Hematology in the CU Anschutz School of Medicine, who will serve as co-principal investigator with Gates Institute Executive Director Terry Fry, MD. The trial is designed to assess the safety, feasibility, and early signs of efficacy of the anti-CD64 CAR T cells in patients who have exhausted conventional treatments. It could pave the way for a new class of personalized therapies for AML and related disorders.
“We are proud to support this work and the incredible scientists leading it,” says Lore Gruenbaum, PhD, Chief Scientific Officer of Blood Cancer United. “We have a long history of providing support for immunotherapy approaches and CAR T therapy in particular, and are very excited that we get to help move this new treatment into the clinic.”
CAR T-cell therapies were first approved by the Food and Drug Administration in 2017 for treatment of certain blood cancers. The initial CAR T therapy, which targeted a receptor called CD19, brought remission in about 75% of patients with acute lymphocytic leukemia. Since then, research has expanded to CAR T cells targeting other receptors, such as CD64, and in other types of cancer.
A standard of care for acute myeloid leukemia are high doses of chemotherapy, which some patients, due to age or other medical conditions, cannot tolerate. In such patients, lower-intensity chemotherapy with venetoclax is recommended, which inhibits BCL-2, a protein that regulates cell death. However, a certain subset of these patients have venetoclax-resistant leukemia; the only option for these patients has been palliative treatment. Fry and Angelos, who are both members of the CU Cancer Center, hope to change that.
“This is a potential new class of therapy that could be used to try to get their disease into remission,” says Angelos. “Ultimately, the real goal here is to try to cure their leukemia.”
The research focuses on developing CAR T cells that specifically target CD64, a protein found in abundance on leukemia cells that are resistant to standard treatment with venetoclax. CAR T cells are engineered immune cells designed to recognize and destroy malignant cells while sparing healthy tissue. The research was fully developed on campus.
“This is a great multidisciplinary effort from a collaborative team of physicians and scientists,” says Angelos, noting that the research originated in the lab of Gates Institute member Craig Jordan, PhD, professor of Hematology in the CU School of Medicine. "Jordan and his team found that these leukemia cells seem to preferentially express this marker.”
That finding opened the door for Gates Institute member Eric Kohler, MD, PhD, assistant professor of pediatrics-Hematology/Oncology and bone marrow transplantation, and his then-fellow Haley Simpson, MD, PhD, to develop a CAR T cell to target the CD64 protein.
Angelos says that the award itself validates the long effort that has led to this point and credits Gates Institute with setting the team up with the tools for success – from regulatory support to biomanufacturing capabilities to create the product just steps away from UCHealth University of Colorado Hospital, where trial participants will receive treatment.
“Many thought leaders in our field reviewed the proposal, and they were impressed by our rationale CAR T cell design and clinical trial strategy that has the potential to have a major impact on the care of patients fighting against AML.”
The clinical trial will be the fifth such trial supported by Gates Institute at CU Anschutz, marking a new achievement for the campus, says Fry.
“It’s been a privilege to watch the collaborative spirit on campus fuel this research,” says Fry. “This project underscores the high caliber of talent at CU Anschutz, where bringing innovative therapies to patients will always be our top priority.”
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