Researchers from Houston Methodist Cancer Center and The University of Texas MD Anderson Cancer Center said they demonstrated a new monoclonal antibody blocked ovarian and pancreatic tumor activity in mice.
For the majority of cases, ovarian and pancreatic cancers do not show early symptoms and therefore go undetected; however, researchers may have established a new immunologic approach to effectively fight these tumors, according to a study published in the Clinical Cancer Research journal.
The researchers developed a monoclonal antibody, which blocks the action of a protein—microfibril associated protein 5 (MFAP5)—secreted by the cells that surround the cancerous tumors. The Octet RED384 system determined the kinetics of binding affinity and the specificity of the antibody clones. Then, ovarian tumor and pancreatic tumor-bearing mouse models were used to test the efficacy of the immunotherapy.
"We found that blocking MFAP5 enhances the effectiveness of chemotherapy treatments and suppresses tumor growth in ovarian and pancreatic cancers, as well as inhibits progression of these two cancers in mice," Stephen T.C. Wong, PhD, from Houston Methodist Cancer Center and co-author of the study, said in a statement. "This new immunotherapy drug targets supporting cells surrounding a tumor rather than just the tumor cells alone. This tumor microenvironment contains newly developed blood vessels and fibrous connective tissue—created through the processes of angiogenesis and fibrosis —that feed and support the tumor."
Functional studies were conducted for 3 hybridoma clones which produced antibodies with high affinity and specificity to MFAP5. The anti-MFAP5 monoclonal antibody demonstrated an ability to down-regulate MFAP5-induced collagen production in cancer associated fibroblasts (CAFs), suppress intratumoral micro-vessel leakiness, and enhance paclitaxel bioavailability in both cancer models, according to the study. The results suggest that treatment strategies based on targeting CAF-derived MFAP5 activities are effective in suppressing cancer.
"MFAP5 promotes fibrosis in ovarian and pancreatic cancers, and fibrosis promotes progression, chemoresistance and reduces survival of people with these cancers,” noted Samuel Mok, PhD, from The University of Texas MD Anderson Cancer Center. “By blocking this secretory protein with an antibody, we can treat the tumor by targeting multiple cellular types—fibroblasts and blood vessels—in the tumor microenvironment."
Targeting MFAP5 demonstrates a new cancer treatment regimen and the researchers are working to designing a humanized anti-MFAP5 antibody for further development as a therapeutic agent for treating ovarian and pancreatic cancers. By the end of next year efficacy and toxicity testing will be completed, followed by a phase 1 clinical trial the following year, the researchers said.
Yeung, Tsz-Lun, Leung, Cecilia S., et al. Anticancer immunotherapy by MFAP5 blockade inhibits fibrosis and enhances chemosensitivity in ovarian and pancreatic cancer [published
online July 22, 2019]. Clinical Cancer Research.