New Life Sciences Startup Shows UCSD Technology Can Boost Immune Response to Cancer in Mice

Xconomy San Diego — 

Research published today has revealed the existence of a new San Diego life sciences company that is working to commercialize anti-cancer technologies intended to boost the immune system to resist tumor growth.

A paper in the journal PloS ONE shows that a gene for a specially engineered form of a protein called CD40 ligand (CD40L), developed by former researchers from UC San Diego, can be used to activate the immune system to fight tumors in mice. The team delivered the gene using nanoparticles created by cancer researchers at the Massachusetts Institute of Technology. The technique can boost the immune response even more when combined with bacterial products called Toll-Like Receptor activators.

The new form of CD40L, called UltraCD40L, is the lead drug candidate for Multimeric Biotherapeutics, a San Diego biotech startup that was founded in February 2008. The startup had made presentations at the Tech Coast Angels’ recent fast pitch competition and Biocom’s investor conference, but was not widely known prior to the publication of the PloS One paper. UltraCD40L was developed at UCSD by Richard Kornbluth, a former associate professor of medicine who left to start Multimeric Bio with Marc Hertz, who is the CEO, and Antonella Vitiello, the startup’s principal scientist.

In an e-mail last night, Kornbluth told me that Multimeric Bio is a pre-seed stage company that has been self-funded by the founders with help from angel investors. (Multimeric refers to a protein with multiple polypeptide chains.)

“From over 9,000 published papers, CD40L has emerged as one of the most powerful immune molecules produced by the body,” Kornbluth says. Researchers haven’t been able to use the molecule as a drug until now because they didn’t realize that it needed to be packaged as aggregated multimeric molecules to be active in the body.

Kornbluth says the easiest way to introduce UltraCD40L, which is a large protein, into the body is to deliver short strands of DNA, called plasmid DNA, that direct its synthesis inside cells. However, the expression of genes from injected DNA is inefficient, especially when the DNA is injected directly into tumors. So the San Diego team collaborated with scientists at MIT’s David H. Koch Institute for Integrative Cancer Research at MIT. The MIT team, which includes Robert Langer (a Boston Xconomist), Gregory Zugates, and Daniel Anderson, have developed biodegradable polymer nanoparticles that encapsulate the DNA and deliver it directly into tumors so that the protein encoded by the gene can be strongly expressed.

The research reported today, Kornbluth says, “describes the use of these polymers to deliver UltraCD40L into large melanoma tumors in mice, causing the tumors to shrink and curing many of the mice completely.”

Kornbluth says the significance of today’s research findings for Multimeric Bio is that it shows the potential application of its UltraCD40L drug candidate in cancer immunotherapy in humans. “The company has applied for grant support to help move this technology to the clinic,” he says, and Multimeric Bio “is especially interested in partnering with a larger company for this purpose.”

Kornbluth says Multimeric Bio is the exclusive licensee of the technology he developed when he was at UCSD. Apart from the cancer immunotherapy work, he says previous reports on UltraCD40L have also shown that is a highly effective vaccine adjuvant, meaning that it can dramatically increase the strength of an otherwise ineffective vaccine. He says it’s currently being tested as part of an HIV vaccine in the monkey model for AIDS.

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