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Recognized as two of the most deadly cancers, ovarian and pancreatic cancers are often referred to as silent killers as they rarely exhibit early symptoms. As a result, they often go unnoticed until it is too late to treat effectively.
Oncology researchers at the Houston Methodist and the MD Anderson Cancer Center at the University of Texas have been vigilant in finding and finding more effective advanced treatments.
In a study published online July 22 in the newspaper Clinical research on cancerCorresponding co-authors Stephen TC Wong, Ph.D., of the Houston Methodist Cancer Center and Samuel Mok, Ph.D., of the MD Anderson Cancer Center at the University of Texas, report that they have discovered a new type of immunotherapy to try to fight against these two deadly cancers. .
Wong, Mok and his colleagues have developed a monoclonal antibody to block the action of a protein secreted by cells surrounding and supporting tumors of ovarian and pancreatic cancers, called MFAP5. This protein is present at high levels in patients with both cancers and badociated with a decreased survival rate.
"We found that MFAP5 blockade enhances the efficacy of chemotherapy treatments and suppresses tumor growth in ovarian and pancreatic cancers, as well as the progression of these two cancers in mice," said Wong, professor of systems medicine and bioengineering at the Houston Methodist Research Institute. "This new immunotherapy drug targets the tumor-surrounding support cells rather than just the tumor cells.This tumor microenvironment contains newly developed fibrous blood vessels and connective tissue – created by the processes of angiogenesis and fibrosis – which nourish and support the tumor. "
MFAP5 has been shown to trigger the formation of these surrounding elements that supply and stimulate the tumor, thereby influencing its growth and spread. Blocking it prevents the formation of new blood vessels and excess tissue in the microenvironment, cutting off blood supply and tumor support.
Mok, professor emeritus of gynecologic oncology and reproductive medicine at MD Anderson, explains: "MFAP5 promotes fibrosis in ovarian and pancreatic cancers, and fibrosis promotes progression, chemoresistance and reduces the survival of people with this cancer By blocking this protein antibody, we can treat the tumor by targeting several cell types – fibroblasts and blood vessels – in the tumor microenvironment. "
Now that they have demonstrated the feasibility of using their monoclonal antibody to target MFAP5 as a new treatment regimen, the researchers are designing and generating a humanized anti-MFAP5 antibody for further development. as a therapeutic agent for the treatment of the ovaries and pancreas. cancers. Wong said he expects it to be ready by the end of the year for efficacy and toxicity tests, followed by a clinical trial. phase I the following year.
"The convergence of biological science, computer science and engineering has allowed us to achieve such a translational discovery," said Wong.
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Other researchers collaborating on this article include Michael J. Birrer from the University of Alabama in Birmingham Alabama; Tsz-Lun Yeung, Cecilia Leung, Kay-Pong Yip and Laura Bover of the MD Anderson Cancer Center of the University of Texas; and Jianting Sheng at the Houston Methodist Cancer Center.
This study was funded in part by NIH grants (U54CA149196, U54CA151668, U01188388, RO1CA133057, RO1CA142832, RC4CA156551, CA177909 and UH2 TR000943); University of Texas MD Anderson, NIH P50CA083639 Research Excellence Program for the Ovarian Cancer Research Program; the US Department of Health and Social Services; Ting Tsung Foundation and Wei Fong Chao; John S. Dunn Research Foundation; Gilder Foundation; the Ovarian Cancer Research Program, US Department of Defense (W81XWH-17-1-0126, W81XWH-17-1-0146 and W81XWH-16-1-0038); and financial support from the Mary K. Chapman Foundation and the Ovarian Cancer Research Fund. The Central Fund for Monoclonal Antibodies is funded by the NCI Cancer Center Support Grant P30CA016672.
For more information on Houston Methodist, visit houstonmethodist.org. Follow us on Twitter and Facebook.
For more information: The anti-cancer immunotherapy blocking MFAP5 inhibits fibrosis and improves chemosensitivity in ovarian and pancreatic cancers. Clinical research on cancer (online July 22, 2019). Tsz-Lun Yeung, Cecilia S. Leung, Kay-Pong Yip, Jianting Sheng, Giulio Draetta, Laura Bover, Anirban Maitra, Michael J. Birrer *, Stephen T. C. Wong * and Samuel C. Mok *
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