Chemist Han Xiao at Rice University and biologist Xiang Zhang at Baylor University and their labs have created BonTarg, an antibody conjugate that delivers medicines to bone cancers and prevents metastasis.
New Antibody Bind Delivers Drugs To Tumors To Slow Metastasis
Their open-access work, published in Science Advances, demonstrates how Xiao’s pClick technology may be used to connect bone-targeting antibodies and medicinal chemicals.
In studies, scientists utilized pClick to link alendronate, a chemical used to treat osteoporosis, with the HER2-targeting antibody trastuzumab, which is used to treat breast cancer, and discovered that it dramatically increased the concentration of the antibody at tumor locations.
The mixture also prevented secondary metastasis from infected organs seeded by bone cancers, according to the researchers.
Bone cancer is extremely difficult to cure, and clinical studies of several therapies for patients with bone metastases have proved unsatisfactory, according to Xiao, who joined Rice in 2017 with support from the CPRIT( Cancer Prevention & Research Institute of Texas ). They believe their plan is a game-changer.
Getting effective medication concentrations to bone cancers has been difficult because bones are hard, their blood artery networks are restricted, and medicines have a tendency to bind to surrounding healthy tissues, according to Zhang.
Bisphosphonates, a type of medicine commonly used to treat osteoporosis, are employed in the new method. Bisphosphonates have a strong affinity for hydroxyapatite, the primary component of hard bone, and they aid in the removal of physical and biological obstacles in the bone microenvironment.
They’re also susceptible to drug binding through pClick, which employs a cross-linker to snap to particular locations on antibodies without the need for hazardous chemicals, enzymes, or UV radiation.
As a consequence, the molecule searches out bone cancers and remains there, allowing the medication time to destroy tumor cells. It also helps that bisphosphonate molecule favor acidic locations, such as bone cancers, where drug concentrations are greater than in surrounding healthy tissue.
The researchers picked breast cancer medicines because, while many people recover from the disease, 20 to 40% of breast cancer survivors later develop metastases to distant organs, with metastases to bone occurring in around 70% of these instances, considerably increasing mortality, they added.
While chemotherapy, hormone treatment, and radiation therapy can reduce or delay bone metastasis in women with bone metastatic breast cancer, they seldom eradicate it, according to Xiao.
According to Xiao, bone is a type of rich soil for cancer cells. If a cancer cell reaches there, it has a very strong probability of growing and migrating to other tissues, such as the brain, heart, liver, or other tissues. That is a terrible circumstance for a patient.
Xiao intends to enter the compound into a clinical study and sees possibilities for bespoke conjugates to treat additional metastasis-prone cancers, such as prostate cancer.
The paper’s co-lead authors are Rice postdoctoral researcher Zeru Tian and Baylor postdoctoral researcher Ling Wu. Rice graduate students Chenfei Yu, Yuda Chen, Axel Loredo, and Kuan-Lin Wu, as well as postdoctoral researcher Lushun Wang, and Baylor postdoctoral colleagues Zhan Xu, Igor Bado, and Weijie Zhang, as well as instructor Hai Wang, are co-authors.
Xiao is a Norman Hackerman-Welch Young Investigator, a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research, and an associate professor of chemistry, bioengineering, and biosciences at the University of Texas at Austin. Zhang- the William T. Butler, M.D., Endowed Chair for Distinguished Faculty. McNair Scholar, the associate director of the Lester and Sue Smith Breast Center, a professor of molecular and cellular biology, and assosiate of the Duncan Comprehensive Cancer Center.
The National Institutes of Health, the Robert A. Welch Foundation, the United States Department of Defense, CPRIT, the John S. Dunn Foundation, the Hamill Foundation, the Breast Cancer Research Foundation, and the McNair Medical Institute all contributed to the study.