“I had absolutely no problem with being the first person,” said Dean, 66. That the drug was developed from a discovery just across the street from where Dean sat Wednesday at Georgia Regents University Cancer Center is another big part of the story.
Dean is the first patient in a clinical trial at the cancer center for a drug called NLG919 that is an inhibitor of the indoleamine 2.3-dioxygenase enzyme, or IDO for short. Cancer center researchers Andrew Mellor and David Munn first reported IDOs role in circumventing the immune system in 1998 as a mechanism by which a fetus is protected from the mother’s immune system.
The enzyme’s role in helping cancer evade the immune system was elucidated by the team in 2002. Now, the inhibitors are poised to become part of other clinical trials battling cancers with few or no good treatments, part of a growing array of what is called immunotherapy for which the cancer center is attracting patients worldwide.
Doing a first-in-humans trial is the mark of a top-flight cancer center, said Dr. Samir N. Khleif, director of the GRU Cancer Center, who is overseeing the trial Dean is participating in.
“This is why people go to Mayo Clinic or to Memorial Sloan Kettering (Cancer Center) or to (M.D. Anderson in) Houston to receive those kinds of therapies,” he said. “Our last patient came from Australia. Because of those clinical trials, particularly because of a clinical trial like this one, we are becoming an international destination.”
Immunotherapy was an ideal area for the cancer center to make its mark, said Khleif, who is a tumor immunologist himself.
“This is a strength of the institution,” he said. “We have excellent scientists here, nationally-recognized scientists. This is one of the hottest areas in cancer currently. I felt that this is an area that can be developed and developed very well so we can have a niche. And actually, now we have a niche.”
That kind of niche expertise will be important when the GRU Cancer Center seeks to be designated by the National Cancer Institute as a Cancer Center because the NCI looks at how a cancer center is contributing in unique and constructive ways, Khleif said. And that is why the trial Dean is participating in is significant on many levels, he said.
“One, it is an immune therapy, within the same program we are developing,” Khleif said. “Second, it is the first time given to humans. Third, it is based on science that has evolved and developed within the institution. This is why it is important.”
In fact, an earlier IDO inhibitor Munn worked with is being offered in combination with chemotherapy in a number of clinical trials at the cancer center for some very difficult to treat cancers. One is attacking a nasty brain tumor called glioblastoma multiforme and was based on work in mice by Dr. Theodore Johnson, a self-styled “homegrown” researcher who worked as a medical and PhD student with Mellor. Immune therapy could be particularly helpful with this brain tumor, which often can’t be fully removed surgically and almost always returns aggressively. Searching out those last remnants would be an ideal use of a revived immune response, Munn said.
“It’s real strength is the fact that it will go in there and look cell by cell,” he said. “It’s evolved to do this. The problem is that it won’t attack the tumor. You’ve got to reverse that tolerant state.”
That is what the IDO and other inhibitors do, It can also help with the resistance tumors build up against chemotherapy agents, Munn said.
“Tumors mutate,” he said. “They develop resistance to chemotherapy or whatever you treat them with. They will develop a new mutation that lets them escape. The immune system knows all about that because bacteria do that and viruses do that. The immune system will sit there and it will attack the bacteria and virus with antigens it has and new mutations will be recognized as a foreign antigen and they will go after that one, too.”
The IDO inhibitors are not the only ones the cancer center is looking at and its growing array and ability to apply its own research and adapt is a strength, Khleif and Munn said.
“That’s one of the reasons it is so important to have a nimble phase 1 clinical trials program,” Munn said. “We’re not the biggest immunotherapy program in the country. We’re a young program and just ramping up. But we can shoot for being the most nimble, the most creative, the most innovative.”
“This is why I believe we are becoming one of the major centers, if not the major center, for the Southeast in immune therapy and tumor immunology,” Khleif said. “When NCI looks at something like this, they look at strength and they look at uniqueness and we have both.”
Dean knows he was in the right spot to be first in line for the new drug. He was first diagnosed with prostate cancer in 1997, had surgery, then had the cancer come back in 2007 in his bladder. He underwent multiple rounds of chemotherapy until he ran out of drugs that would work.
“We were running out of options,” Dean said.
“There were no more options,” said his wife, Marcia.
But then they were referred to the GRU Cancer Center and he was the first to qualify for the drug. He is on his second cycle and said he feels pretty good, other than a little fatigued. The cancer, which had spread to lymph nodes in his neck, had left him with the feeling of a lump in his throat and that seems to have eased, but a scan next month will give them a better idea.
Compared to the chemotherapy he was taking, “I feel a whole lot better doing this,” Dean said.