A research team from Emory University and Metaclipse Therapeutics Corp. is developing a new cancer vaccine immunotherapy targeting triple-negative breast cancer (TNBC). This aggressive type of breast cancer is very difficult to treat because it presents a variety of gene mutations both within each tumor and among different individuals, and thus presents no defined targets for drugs or vaccines to attack. TNBC is more common among young, African-American women, and five-year survival rates are lower than for other types of breast cancers.
The vaccine under development uses tumor membrane vesicles (TMVs) prepared from the patient's own tumor. The vaccine is then modified by incorporating immunostimulatory molecules (ISMs) through a novel protein transfer method. Use of autologous tumor tissue from the patient incorporates the patient's unique immune signature into the vaccine design and overcomes the issue of heterogeneity within a single tumor and patient-to-patient variation in gene mutations.
Metaclipse was previously awarded an NIH Phase I SBIR grant to further validate the vaccine technology in a mouse model of TNBC. The company has also received seed grants from the Georgia Research Alliance Venture Lab program and the Coulter Foundation.
Based on promising preclinical data, Emory and Metaclipse have now been jointly awarded a $2.4 million, five-year R01 grant from the National Cancer Institute of the National Institutes of Health for research that will advance this vaccine immunotherapy approach and aid in designing a clinical trial strategy for this TMV-based immunotherapy in TNBC patients.
Co-principal investigators of the grant are Periasamy Selvaraj, PhD, Emory professor of pathology and laboratory medicine and Winship Cancer Institute member, and Christopher Pack, PhD, director, preclinical research, at Metaclipse Therapeutics Corporation. Selvaraj is part of Winship's Discovery and Developmental Therapeutics Program.
"Recent FDA approval of anti-cancer immunotherapy drugs for metastatic disease is a promising development that validates immune stimulation as an effective way to control or prevent metastatic disease. However, these drugs are only effective in a subset of patients. Many cancers, such as breast cancer, do not respond well to these new drugs, which suggests the need for a personalized approach," says Selvaraj.
"Our preclinical studies suggest that patients who are resistant to currently approved immune checkpoint inhibitor therapy may respond if such therapies are combined with our personalized immunotherapy approach. We anticipate that this will extend the benefit of approved immunotherapy products to a wider patient population," commented Pack.
For their ongoing studies, the researchers will use a new mouse model that more closely mimics the human immune system. Studies using both mouse tumor tissue and human TNBC tumor tissue will compare standard-of-care chemotherapy treatments alone and combined with the TMV-based patient-specific immunotherapy.
The knowledge from these mouse studies will be used to design a human clinical trial strategy for this TMV-based immunotherapy in TNBC patients.
Winship Cancer Institute breast cancer oncologist Keerthi Gogineni, MD, assistant professor of hematology and medical oncology, and Winship scientist Xiaoxian (Bill) Li, MD, PhD, assistant professor of pathology, will be collaborating on the project by providing access to tumor tissue from breast cancer patients.
This research is funded by NCI grant # R01-CA202763.
Metaclipse has an option agreement on the core vaccine technology from Emory University, invented by Dr. Selvaraj. Emory and Dr. Selvaraj could benefit financially from the commercial success of related products. This relationship has been reviewed and approved by Emory University within its conflict of interest guidelines.