Smaller antibodies are better?
For a potentially life-saving cancer drug, smaller may be better. Scientists have shown that a miniature version of the commercial monoclonal antibody Herceptin is not only as effective as the original molecule in killing tumors, but could also potentially avoid drawbacks such as antibody immunogenicity, poor tissue penetration, and problems with manufacture. The results suggest that antibody mimics may provide a promising new avenue in the design of antibody-based therapies.
Herceptin is an anticancer treatment that targets breast tumor cells expressing the HER2 gene. The drug is a member of a class of compounds called monoclonal antibodies that inhibit the growth of tumors by binding to their receptors and blocking the binding of growth factors, which otherwise would cause the cells to divide and multiply.
In the present study, Mark Green and Ramachandran Murali set out to assess what portions of an antibody are needed to retain tumor cell binding capacity. By modeling small protein molecules (peptides) so that they resemble only the part of the antibody known to bind to tumor receptors, they created several miniature antibody mimics. When these peptides were tested for biological activity, they found that one of the peptides, which had two different structural forms, showed moderate activity, with one form performing better than the other. In cell culture, the latter peptide was found to bind to receptors encoded by genes related to HER2, allowing them to inhibit the growth of tumor cells. Experiments in mice also showed that the peptide went to the tumors that contained the HER2 gene and inhibited growth.
Contact
(Author)
Dr. Ramachandran Murali
University of Pennsylvania School of Medicine
Department of Pathology and Laboratory Medicine
M163 John Morgan Building
36th and Hamilton Walk
Phildelphia, PA 19104-6055
[email protected]
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#1. Smaller is better for antibodies? (Research paper p. 194).
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