Scripps Research Institute scientists have found a way to target and destroy a type of cancerous cell, and these findings may lead to the development of new therapies to treat lymphomas, leukemias and related cancers.
Scripps Professor James Paulson has been studying glycoproteins, which are proteins decorated with sugars. And in the new research, he and his colleagues sought to use these proteins to attack B cell lymphoma. Because of his previous research, Paulson knew that B cells had a unique receptor protein on their surfaces that recognized certain sugars found on glycoproteins. He hypothesized that the team might be able create a viable potential therapeutic that carried these same sugars to identify and target these cells.
The scientists attempted this by combining two types of molecules into one. One part of the potential therapeutic was composed of a specialized sugar (ligand) recognized by the B cell receptor, called CD22. This was attached to the surface of the other portion, a nanoparticle called a liposome, loaded with a dose of the chemo drug doxorubicin. The team used a nanoparticle formulation of doxorubicin called Doxil.
Normally Doxil is passively delivered to tumors, and the drug slowly leaks out to kill the tumor. But by decorating the nanoparticles with the CD22 ligand, the team made them into a type of Trojan horse that is actively targeted to and taken up by human lymphoma B cells, carrying the drug inside the cell. The team administered their new compound to immune-compromised mice that had been infected with B cell lymphoma cells. The team used two different formulations of the molecule, one decorated with two percent ligands, the other with five percent. The mice received only one dose. No mouse in the control group lived to the end of the 100-day trial, but five of the eight mice receiving the higher ligand dose of the compound survived.
"[The method] worked immediately," says Paulsen. "We are very interested in moving this technology forward to see if it would be applicable to treatment of humans and to investigate other applications for this kind of targeting."
The team is now working to further improve the drug platform, looking for ways to increase the specificity of B cell targeting as well as exploring the technology's use with other chemotherapy agents.
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