Reshef did not develop the drug that was given to the tugboat captain, a patient in a national trial. That same morning, however, the New England Journal of Medicine published his article on novel bone marrow work that, for the first time, showed early success in humans.
Immune cells seek out and destroy anything foreign, including organs they don't recognize. Organ transplants require toxic drugs to suppress the immune system, leaving the body vulnerable to infections.
Reshef's team managed to manipulate the homing function of the immune cells so that they simply did not seek out the body parts most at risk.
New use for HIV drug
The concept had been around for a while, but no one had got it to work well, even in mice. Reshef realized that an existing HIV drug happened to have the properties that might influence the cells' "traffic cop" function.
Excited, he mentioned it in the hallway one day to the head of his laboratory.
"As soon as I heard it, it blew me away, and I knew that we needed to study it in the lab," said Robert H. Vonderheide, one of two senior authors of the paper.
The other senior author is David L. Porter, a clinical researcher who treats patients as head of the Penn cancer center's blood and marrow transplantation program. Reshef shuttled back and forth between scientist and clinician as his idea was fleshed out, tested, and designed for human application.
"It is a tripartite kind of relationship," Porter said, with labwork leading to clinical treatments and then back to the lab for improvement. "And you learn so much more about the treatment that way."
Research to treatment
"Translational research" has become a buzzword over the last decade.
Many centers that aim to "translate" laboratory research into treatment that works for patients have opened around the country.
"Penn is out in front in many ways in the translational research arena," said Francis Collins, director of the National Institutes of Health, who was in Philadelphia for a conference on Friday. "The collection of researchers and ideas right here at Penn is really breathtaking in terms of the creativity, the energy, the science that they are producing."
Relationships play a key role, said Roger Strair, a blood-cancer and bone-marrow expert at the University of Medicine and Dentistry of New Jersey: "The people who are very good at what they do are also very good at working together."
They have had a good year.
Last August, Porter was part of a team led by Carl June that reported it had genetically engineered powerful immune cells, called T cells, to recognize, attack and then stand guard against chronic lymphocytic leukemia. Although only three patients who had failed standard therapies were treated with the designer T cells, all three went into lengthy remissions. Never before in published experiments had engineered T cells multiplied - and then persisted - enough to be so effective in patients.
And two months ago, June and colleagues reported the long-term results of their experimental T-cell gene therapy for HIV, the virus that causes AIDS. It had carried on without bad side effects for up to 11 years in 41 of 43 treated patients.
June is a well-known immunologist and gene therapy pioneer. He also is director of translational research at the Abramson Center.
"When he hired me," said Vonderheide, the associate director and senior science author on last week's paper, "he said, 'Why don't you think about the immunology of bone marrow transplants?' "
Vonderheide earned a doctorate in immunology at Oxford and had once planned a career as a bench scientist. He said he was so struck by the life-saving potential of his field that he "went to medical school to learn how to translate these ideas to patients."
Immune system is key
His lab began early on to explore what is now the hot field of manipulating the immune system to deal with various cancers in a number of ways, from shrinking tumors, to preventing them with vaccines, to "trafficking" cells away from organs they would instinctively attack.
Those attacks are known as "rejection" when organs like the liver and kidney are transplanted into a patient and seen as alien tissue.
Donated bone marrow transplants raise a similar problem for the opposite reason. The risky procedure, often a last resort, imports an entirely new immune system, hopefully with the ability to defeat a cancer that the patient's own system could not. But the donated immune system sees the patient's entire body as foreign, and attacks.
The damage, known as graft-versus-host disease, is by far the most serious complication of donated marrow transplants, occurring in about 50 percent of patients.
Reshef, who arrived at Penn as a fellow in 2007 and is now an assistant professor at the medical school, became interested in bone marrow during his training in Israel, where he grew up. He was already looking into the possibility of "trafficking" immune cells when he read a 2009 paper that energized researchers around the world: A gay American man in Germany, dubbed the "Berlin Patient" by the New England Journal, had been essentially "cured" of AIDS.
The patient had received a bone marrow transplant in Europe to fight leukemia. The donated marrow happened to have a gene deletion in a receptor on cell surfaces that is known to be involved with how cells travel.
That CCR5 receptor also is how some forms of HIV break into immune cells - and a drug on the market since 2007 treats HIV by blocking those receptors.
The Berlin Patient article "was in fact the inspiring moment when we realized that CCR5 could have this clinical role," Reshef said - not just in mice but in humans, and not just for HIV.
That realization normally would take millions of dollars and years of research to develop into a drug, if it ever did. But the Pfizer drug, known as maraviroc (pronounced ma-RA-vi-roc), was already being used; it had been proven safe; potential dosages were known.
Reshef worked in the lab, watching as T cells in a test tube moved through a membrane - and didn't move when he added maraviroc to the mix. Working with the other translational researchers, he designed a human trial.
The results, published Thursday, showed that when 38 bone marrow transplant patients got maraviroc along with the immunosuppressant regimen, far fewer than expected developed severe graft-versus-host disease. A national, randomized study is on the drawing boards.
Although all the key people on the translational research team are trained as both scientists and clinicians, Reshef more than anyone straddled the line, relying on mentors on both sides.
"This is a really good example," said Porter, of how Penn translates research from lab to patient, and grooms the next generation of physician-researchers like Reshef.
Contact Don Sapatkin at 215-854-2617 or firstname.lastname@example.org.
Allyn Gaestel contributed to this article.