Antibody with engineered peptide targets bone metastasis
Enhanced breast cancer drug could halt spread

Date:
January 24, 2022
Source:
Rice University
Summary:
A moderate amount of a peptide-enhanced cancer drug goes a long
way in treating breast cancers that metastasize to the bone.



FULL STORY ==========================================================================
A moderate amount of a peptide-enhanced, biological cancer drug goes a
long way in treating breast cancers that metastasize to the bone.


==========================================================================
A study by scientists at Rice University and Baylor College of Medicine demonstrated the effective treatment of such cancers in rodent models,
bringing hope for new therapies to treat bone metastases.

The open-access study, to appear on the cover of the American Chemical
Society journal ACS Central Science, advances techniques pioneered by
Rice chemist Han Xiao and his co-author at Baylor, biologist Xiang Zhang.

They discovered through extensive testing that engineering "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 of the drug compound doesn't make it better. The drug contains an engineered peptide
that finds and binds to bone, but worked best when a moderate amount
was delivered.

"The negative charge of the peptide has an affinity for the positively
charged bone cancer niche," said Xiao, whose lab created a library of
modified antibodies for testing. "We found the therapeutic efficacy
is best with the antibody that has mediocre affinity. That's a really
big discovery." As many as 40% of breast cancer survivors eventually experience metastases to distant organs, most often to the bone. Xiao
noted bone tumors are notoriously difficult to treat, given the hard
nature of the material and its limited vascular network. Delivering a
low amount of a drug, he said, can also help tumors develop resistance.

The study showed that peptide-enhanced antibodies also prevented secondary metastases from bone to other organs.

The researchers hope to find collaborators to move the strategy toward
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 alumna Ruchi
Gupta, now a graduate student at Yale School of Medicine.

Xiao is the Norman Hackerman-Welch Young Investigator and an assistant professor of chemistry, biosciences and bioengineering. Zhang is an
associate professor of molecular and cellular biology and the McNair
Scholar in the Lester and Sue Smith Breast Center at Baylor.

The Cancer Prevention Research Institute of Texas (RR170014), the
National Institutes of Health (R35-GM133706, R21-CA255894, R01-AI165079, CA221946), the Robert A. Welch Foundation (C-1970), the 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.

========================================================================== Story Source: Materials provided by Rice_University. Original written
by Mike Williams. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Zeru Tian, Chenfei Yu, Weijie Zhang, Kuan-Lin Wu, Chenhang Wang,
Ruchi
Gupta, Zhan Xu, Ling Wu, Yuda Chen, Xiang H.-F. Zhang, Han
Xiao. Bone- Specific Enhancement of Antibody Therapy for Breast
Cancer Metastasis to Bone. ACS Central Science, 2022; DOI:
10.1021/acscentsci.1c01024 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220124204258.htm

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