Researchers at Baylor College of Medicine and Rice University have received a $2.3 million Breakthrough Award from the Department of Defense Congressionally Directed Medical Research Programs to develop a novel NanoGel antibody therapy that targets ER+ breast cancer that has metastasized to bone.
“Current treatments work well for ER+ breast cancer, but 20-40% of survivors later experience recurrence in other organs,” said Dr. Xiang H.-F. Zhang, director of the Lester and Sue Smith Breast Center and professor of molecular and cellular biology at Baylor. “Antibody-based therapies are a promising approach for treating breast cancer that has metastasized, but this approach has not worked as well for cancer that spreads to the bones. More effective treatments are needed for bone metastases.” Zhang also is William T. Butler, M.D., Endowed Chair for Distinguished Faculty and a McNair Scholar at Baylor and a member of the Dan L Duncan Comprehensive Cancer Center.
To address this problem, the team will engineer an antibody therapy using NanoGel, a polymer-based nanoparticle designed for drug delivery. The NanoGel will release antibodies when it encounters the acidic environment of the bone. The antibodies will target E-cadherin proteins in ER+ cancer cells, which the Zhang lab has previously shown plays a role in tumor growth in the bone.
“The platform’s key advantage lies in its ability to encapsulate the antibody within the NanoGel during circulation and ensure its controlled release in the bone metastatic niche, which benefits from a lower pH for optimal delivery,” said Dr. Han Xiao, director of the SynthX Center and associate professor of chemistry, biosciences and bioengineering at Rice and a CPRIT Scholar in Cancer Research. “This strategy also holds potential for application with other therapeutic antibodies, including those used in immunotherapies.”
In this project, the researchers will test how well the NanoGels locate and bind to tumors in the bone. They will examine the therapy’s effectiveness against ER+ breast cancer cells in mouse models. The researchers hope the therapy also will be effective in preventing bone micrometastases from spreading to other organs.
This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs and the Defense Health Agency J9, Research and Development Directorate, or the U.S. Army Medical Research Acquisition Activity at the U.S. Army Medical Research and Development Command, in the amount of $2.3 million through the Breast Cancer Research Program, under Award No. BC240241. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.
This work also is part of the strategic collaboration between Baylor College of Medicine’s Dan L Duncan Comprehensive Cancer Center and the Rice SynthX Center. This year, the centers jointly awarded their first innovation seed grants to three Rice-Baylor teams, supporting groundbreaking cancer drug and technology development through integrated research in organic chemistry, chemical biology, and material chemistry.
