Dana-Farber Launches First Clinical Trial of Memory-Like Natural Killer Cells in Ovarian Cancer
核心洞察
Dana-Farber Cancer Institute initiates a clinical trial to assess memory-like natural killer (NK) cell therapy in recurrent, platinum-resistant ovarian cancer (搜索) patients.
The Phase 1B study will evaluate the safety, tolerability, and anti-tumor activity of NK cells modified to enhance memory function and persistence.
Patients receive chemotherapy (搜索) to optimize the tumor microenvironment before the modified NK cells are infused directly into the peritoneal cavity.
Dana-Farber Cancer Institute has launched a clinical trial to evaluate a novel immune cellular therapy using memory-like natural killer (NK) cells in patients with recurrent, platinum-resistant ovarian cancer (搜索). This Phase 1B study marks one of the first in the U.S. to investigate the safety, tolerability, and anti-tumor activity of these specialized NK cells in ovarian cancer.
Memory-Like NK Cells: A Novel Approach
Natural killer cells are crucial components of the innate immune system, capable of recognizing and destroying cancer cells. However, unlike T cells, conventional NK cells lack long-term persistence and immunological memory. Researchers at Dana-Farber, led by Rizwan Romee, MD, have developed memory-like NK cells that are modulated in the lab to enhance their memory function, proliferation, and persistence within the body.
Preclinical studies in ovarian cancer (搜索) cell lines and mouse models have demonstrated that these memory-like NK cells exhibit strong anti-tumor responses. Encouraging initial results have also been observed in studies involving memory-like NK cells in other cancer types, such as acute myelogenous leukemia (搜索) and head and neck cancers.
Trial Design and Objectives
The clinical trial, led by Rebecca Porter, MD, PhD, a gynecologic medical oncologist at Dana-Farber, will enroll 12-18 patients with recurrent, platinum-resistant ovarian cancer (搜索). The primary objectives are to determine the safety, tolerability, and maximum tolerated dose of the memory-like NK cells. Secondary endpoints will assess the efficacy of the therapy.
"Novel and more effective therapies for our patients with recurrent ovarian cancer (搜索) are very much needed," said Dr. Porter. "Unfortunately, immune checkpoint inhibitors (搜索) in ovarian cancer have limited efficacy and standard of care for patients with platinum resistant ovarian cancer remains chemotherapy (搜索). We hope this study provides insights into a novel approach to activating an anti-tumor immune response in patients whose ovarian cancer has progressed on other therapies."
Treatment Protocol
The trial involves harvesting NK cells directly from the patient, modulating them in the lab to generate memory-like properties, and then administering them back to the patient. The modified cells are infused directly into the peritoneal cavity, where ovarian tumor cells are commonly located. Patients also receive chemotherapy (搜索) to create a more favorable tumor microenvironment for the infused NK cells.
To be eligible for the study, patients must have received at least three prior lines of systemic therapy and have platinum-resistant disease. Eligible histologies include high-grade endometrioid or high-grade serous ovarian carcinoma.
The Need for New Therapies in Ovarian Cancer
Epithelial ovarian cancer (搜索) is a significant cause of cancer-related mortality in women. Most patients are diagnosed with advanced disease, leading to a 5-year survival rate of less than 50% across all stages, which decreases to approximately 30% for patients with advanced disease. The limitations of current treatments, including immune checkpoint inhibitors (搜索), highlight the urgent need for innovative therapeutic strategies.
Future Directions
Romee’s lab is also working on arming memory-like NK cells with a novel chimeric antigen receptor to further enhance their tumor-fighting capabilities. Clinical studies involving these CAR-NK cells are expected to begin soon.
"I am firmly believe NK cell based therapies have a great potential to improve the outcomes of patients with advanced ovarian cancer (搜索) and also allow us to further improve our knowledge about the underlying biology of this disease which will be critical for our future therapeutic strategies for these patients," added Romee.
The study is funded by Team Ovarian Cancer (搜索) and the PHASE One Foundation.