Six out of the ten best selling drugs are proteins called monoclonal antibodies. But the prospect for monoclonal antibodies was not always so bright. It took a decade after their discovery in 1975 before they found any clinical use, even then it was very limited use for organ transplant rejection. It was a full twenty years before their first wide spread use in cancer. One of the first cancer therapies using antibodies, Herceptin approved in 1998, keeps many breast cancer patients alive today.
Dennis Slamon, worked for more than a decade in his lab at the University of California, Los Angeles, to get Herceptin tested, approved and marketed by Genentech. That story, told in “The Emperor of All Maladies,” shows him working against skeptics and critics often with scant financial support. Now, he has turned that laser focus on finding a therapy that can seek out and destroy cancer stem cells from a broad array of cancers—an effort he began in earnest some five years ago with an early disease team grant from CIRM.
That early CIRM grant let his team test several different compounds alone and in combination with standard therapies to settle upon one drug that targets a protein called PLK-4, a specific kinase that is found in many cancer stem cells. CIRM now funds an early phase clinical trial testing that drug in several different solid tumors. The University Health Network in Toronto, partnered with CIRM in supporting the early work, and now also funds another clinic site for the same trial at the Princess Margaret Hospital in Toronto.
All doses safe so far
So far, seven groups of patients made up of three patients each, have been given increasing doses of the drug. The Slamon team suspected that the early doses administered in the trial were likely to be too small to be effective but the Food and Drug Administration appropriately insists on the demonstration of safety first for new
therapies. So far in the study none of the groups have shown any toxicity and Slamon thinks, based on the animal data that they are now near a dose where they could see patient tumors responses. Since each group has to be monitored for four weeks before the next group can be treated it has been nearly a year since the trial began, but Herceptin showed Slamon has the stamina to stick with a therapy that makes sense.
One of the early participants in the trial, Frank Gonzalez, knew he would probably be getting a dose too low to be effective, but felt it was valuable to participate for the potential long term outcomes of the therapy. (link to his story and video)
Second trial targets leukemia stem cells
CIRM funds a second clinical trial that targets a protein broadly found on cancer stem cells, with the current trial treating leukemia. This therapy, an antibody being tested at the University of California, San Diego, targets a protein called ROR1. When the antibody blocks that protein it prevents the cancer stem cells from proliferating and encourages them to die. We at CIRM are proud of the name the team gave the antibody, Cirmtuzumab. This trial, too, was required to start at a very low dose to guarantee safety and has slowly escalated the dose with the expectation of the trial continuing for another year. One of the lead researchers on that trial, Catriona Jamieson, also thinks they may be near a therapeutic dose where they may see tumor response.
Many companies have jumped into the field developing traditional drugs and antibodies targeting cancer stem cells. As always it is nice to have colleagues working on many different routes to the same goal. It makes sense that some of these should work. Patients fearful of their doctor telling them “it’s back” deserve nothing less.