UAB Comprehensive Cancer Center Magazine Winter 2018 2018 Volume XXXIII Number 3 - Page 19

First in humans LoBuglio: “We were in the vanguard looking at use of monoclonals in humans. There had been no mouse monoclonal studies in humans, except small, individual studies in Europe. Our group did the first mouse monoclonal antibody study in the United States with a formal protocol. There had been considerable expertise at UAB in basic immunology. We added a radioisotope labeling person, and a physician to lead the trials and lab people who could do correlative studies.” Mansoor Saleh. Photo courtesy UAB Archives. Andres Forero, M.D., trained as a fellow with LoBuglio in the 1980s, and has spent much of his career at UAB. He is now a senior scientist and director of the Breast Cancer Program at the UAB Comprehensive Cancer Center. Andres Forero: “Dr. LoBuglio was one of the first people who saw the future of monoclonal antibodies. Thirty years ago, there were two ways to go in cutting-edge cancer research: one was vaccines, and the other was Mabs. One of the nice things about Dr. LoBuglio is that he was interested in both and worked in both areas. Vaccines, unfortunately, have failed dramatically. Not a single one is available today. But the Mab pathway has become one of the most successful stories in the treatment of cancer.” Saleh: “There was a company that made antibodies against a target that seemed to be prevalent on tumor cells. They were not tumor- specific, because those targets were also on normal cells, but we had to at least give it a try. We were able to show that, yes, a patient can receive a mouse Mab targeting the tumor. But the half-life of the mouse antibody was very short — a few hours. “We could give one dose with no problem. By the second dose, the patient had already made an immune response to the mouse, so by the time you gave the third dose it was destroyed very quickly. You really couldn’t use this for therapeutic purposes, although you could use it for imaging.” LoBuglio: “Our paper said that mouse monoclonal antibodies were impractical, and defined regions that produced the immune response and said that was the area we had to get rid of. So in collaboration with a company called Centocor, we developed a genetically engineered monoclonal antibody that was part mouse and part human.” # K N O W U A B C C C • “We did the first trial in a human and it worked well. Our conclusion was that these genetically engineered antibodies were what had to be used for efficacy.” Alber t LoBuglio, M.D. U A B . E D U / C A N C E R 17