Berkeley leading the way on new approaches to cancer immunotherapy
March 30th, 2015
A newly announced biotech deal shows how basic research at UC Berkeley is leading to new therapeutic approaches for cancer.
Novartis has just announced a major $750M partnership with Berkeley-based Aduro BioTech to develop a new class of molecules, called CDNs, as a potential immunotherapy for cancer. These molecules were first discovered in bacteria, but the basic research showing how CDNs activate the human immune system was largely done in labs associated with the Cancer Research Laboratory (CRL) here at UC Berkeley. Building off this basic research, Aduro has shown, in preclinical studies in mice, that CDNs can potently activate the immune system to attack and eliminate a variety of aggressive tumors. These exciting studies were presented last year at the American Association for Cancer Research meeting in San Diego, ultimately leading to the recently announced deal with Novartis to further develop these compounds for use in humans.
Although it is still too early to know whether CDNs will ultimately be successful in treating human tumors, the story of their discovery provides yet another example of how basic research at UC Berkeley has led to new conceptual approaches to cancer therapy. CDNs, or cyclic-di-nucleotides, were originally discovered as small molecules produced by bacteria. For many years, CDNs were thought to function solely in bacteria, and their potential value in cancer immunotherapy was not appreciated. This started to change with a 2007 paper from the Karaolis Group in Maryland, showing that CDNs could activate immune cells. However, it was still unclear how CDNs were working to activate the immune system. In 2009, the Vance Lab at UC Berkeley published a paper in the Journal of Experimental Medicine showing that delivery of CDNs into mouse cells activated the mouse cells to produce a potent immunostimulatory molecule called type I interferon. Subsequently, the Portnoy Lab, also at UC Berkeley, showed in a paper published in Science, that the bacterial pathogen Listeria monocytogenes activates the immune system of mice by secretion of CDNs. It remained a mystery how CDNs activated the immune system until 2011, when the Vance and Portnoy Labs collaborated on a paper published in Infection and Immunity to show that the interferon response to CDNs requires a host protein called STING. The Vance Lab then published a paper in Nature that demonstrated CDNs directly bind to STING, providing the key molecular target for these potent immunostimulatory molecules. Most recently, the Vance and Hammond Labs at UC Berkeley showed in a 2013 paper in Cell Reports that special “non-canonical” CDN variant molecules were particularly potent activators of human STING.
The original motivation for the research on CDNs was driven by curiosity about how the immune system is activated in response to bacterial infection. The Cancer Research Laboratory believes this story provides yet another outstanding example of how basic curiosity-driven research can ultimately lead to a promising new approach for treatment of human cancer.
