August 28, 2006
Antibody-Dendrimer Combo Penetrates Cancer Cells Faster Than Antibody Alone
Herceptin, one of the first generation of targeted cancer therapies, is a monoclonal antibody that binds to a specific protein, known as HER-2, found in abundance on the surface of certain types of breast cancer cells. Taking a cue from the success of this agent, investigators at the University of Michigan have used a similar HER-2-binding monoclonal antibody as a targeting agent for a dendrimer designed to deliver anticancer drugs into tumor cells. Dendrimers are highly branched, spherical polymers that form well-defined, biocompatible nanoparticles.
James Baker, Jr., M.D., who heads a National Cancer Institute Alliance for Nanotechnology in Cancer Platform Partnership team, led this effort to combine the targeting and therapeutic properties of an anti-HER-2 monoclonal antibody with the drug delivery capabilities of a dendrimer. The results of this study appear in the journal Bioconjugate Chemistry.
Initial tests with the antibody-dendrimer combo showed that it bound avidly to cultured tumor cells that express the HER-2 protein on their surface but not to other tumor cells that lack the HER-2 protein. While the investigators expected this result, they were surprised to find that the antibody-dendrimer conjugate quickly crossed the cell membrane of the HER-2-positive cells, while antibody not attached to the dendrimer nanoparticle remained bound to the outside of the cell membrane.
Subsequent experiments in tumor-bearing animals yielded similar results. While both the antibody and antibody-nanoparticle conjugate were able to find and bind to tumors, only the antibody-nanoparticle conjugate accumulated inside tumor cells. These findings suggest that an antibody-targeted dendrimer has the potential to be an even better anticancer therapy or imaging agent than the antibody alone.
This work, which was supported by the National Cancer Institute, is detailed in a paper titled, “HER2 specific tumor targeting with dendrimer conjugated anti-HER2 mAb.” This paper has been published online in advance of print publication. An abstract is available at the journal’s website.