Peptide-Boosted Antibody Therapy May Help Treat Breast Cancer Bone Metastases
A moderate amount of a peptide-enriched biologic cancer drug goes a long way in treating breast cancers that metastasize to bone.
A study by scientists at Rice University and Baylor College of Medicine has demonstrated the effective treatment of these cancers in rodent models, providing hope for new therapies to treat bone metastases.
The open-access study, which will appear on the cover of the journal American Chemical Society ACS Central Science, advances techniques pioneered by rice chemist Han Xiao and his co-author at Baylor, biologist Xiang Zhang.
They found, through extensive testing, that designing bone-homing peptides and attaching them to a common breast cancer drug, the antibody trastuzumab, effectively targets and attacks bone tumors.
The researchers reported their surprise that injecting more drug compound did not improve it. The drug contains a modified peptide that finds and binds to bone, but works best when a moderate amount is administered.
The negative charge of the peptide has an affinity for the positively charged bone cancer niche. We found that the therapeutic efficacy is better with the antibody which has poor affinity. It’s a great discovery.”
Han Xiao, rice chemist
Xiao’s lab has created a library of modified antibodies for testing.
Up to 40% of breast cancer survivors eventually develop metastases in distant organs, most often in bone. Xiao noted that bone tumors are notoriously difficult to treat, given the hard nature of the material and its limited vascular network. Giving a small amount of a drug, he said, can also help tumors develop resistance.
The study showed that the peptide-boosted antibodies also prevented secondary metastases from bone to other organs.
The researchers hope to find collaborators to evolve the strategy into human trials.
Rice postdoctoral fellow Zeru Tian and graduate student Chanfei Yu are co-lead authors of the paper. Co-authors are Baylor postdoctoral fellows Weijie Zhang and Zhan Xu and postdoctoral associate Ling Wu; Rice graduate students Kuan-Lin Wu, Chenhang Wang and Yuda Chen, and Rice alumnus Ruchi Gupta, now a graduate student at Yale School of Medicine.
Xiao is the Norman Hackerman-Welch Young Investigator and Assistant Professor of Chemistry, Biosciences, and Bioengineering. Zhang is an associate professor of molecular and cellular biology and a McNair Fellow at Baylor’s Lester and Sue Smith Breast Center.
Cancer Prevention Research Institute of Texas (RR170014), National Institutes of Health (R35-GM133706, R21-CA255894, R01-AI165079, CA221946), Robert A. Welch Foundation (C-1970), Department of Defense (W81XWH -21-1-0789, DAMD W81XWH-16-1-0073), the John S. Dunn Foundation and a Hamill Innovation Award supported the research.
Tian, Z., et al. (2022) Bone-specific enhancement of antibody therapy for breast cancer bone metastases. AEC Core Sciences. doi.org/10.1021/acscentsci.1c01024.