Ibalizumab, a monoclonal antibody for treating Multidrug resistant HIV infection

A new biologic medication – the first for HIV – is showing promise in treating patients with multidrug resistance, according to phase 3 research being presented at IDWeek 2016™. Administered intravenously once every two weeks, ibalizumab is a biologic medication called a monoclonal antibody, a genetically engineered molecule that coats immune system cells to protect them from HIV entry. Eighty three percent of patients with multi-drug resistant HIV (MDR HIV) had a virologic response to the drug, according to the study.

When taken as directed, combination treatment called antiretroviral therapy (ART) is highly successful in combatting HIV. However, of the 1.2 million Americans who have HIV, about 10,000 have MDR HIV, meaning they are resistant to all medications used to treat HIV.

“This is the first drug in a long time for patients with multidrug resistance,” said Jacob Lalezari, MD, lead author of the study and medical director for Quest Research, a division of eStudySite, San Franscisco. “This therapy showed good activity in patients who were resistant to everything else, which is very exciting for these vulnerable patients and those who care for them.” He noted that ibalizumab is the first of what promises to be many long-acting anti-viral treatments. While most ART therapy is once a day, researchers are testing medications that are taken less frequently, which will make it easier for patients to take them as prescribed.

The study included 40 patients with MDR-HIV who had been infected with HIV for an average of 21 years and had been treated with many medications. More than one in four (28 percent) had been treated with 10 or more HIV medications. All were given ibalizumab: 35 percent required an additional investigational medication due to resistance to all HIV medications. Most patients benefitted after seven days of treatment: 24 (60 percent) achieved a significant decrease in viral load of 1.0 log10 or greater and 33 (83 percent) achieved a decrease in viral load of 0.5 log10. The average decrease in viral load after seven days of treatment was 1.1 log10. During the control period at the beginning of the study before ibalizumab was added, only one patient (3 percent) had achieved a significant decrease in viral load on the existing ART regime. After one week, all patients continued with ibalizumab and began taking optimizing HIV medications as part of the ART regimen. The combination therapy varied by patient.

“This drug benefits a small but challenging population of HIV patients who are highly treatment experienced,” said Daniel R. Kuritzkes, MD, chief of the Division of Infectious Diseases at Brigham and Women’s Hospital and professor of medicine at Harvard Medical School, Boston. “This will not be a first- or second-line therapy for those who are infected with HIV, but it may be helpful for certain patients.”

The bi-weekly regimen is beneficial for these patients, said Dr. Lalezari. “There’s higher compliance because they have a place where they can go and are cared for, and it really works for them,” he said.
Some patients are infected with a multidrug resistant form of HIV, but most others develop resistance after periods of time when they are unable to take their ART medication as directed, he said.

Research presented at  IDWeek 2016™.
Research funding by TaiMed Biologics, the manufacturer of ibalizumab.
Adapted from press release by Infectious Diseases Society of America

University of Iowa’s hybridoma bank, a national treasure

The Developmental Studies Hybridoma Bank at the UI was created by the National Institutes of Health in 1986 to store and distribute laboratory-produced proteins used for cancer research and other scientific pursuits. University of Iowa biology professor David Soll has run the bank for the past 20 years as an independent nonprofit entity, creating, storing, and distributing these proteins, called monoclonal antibodies, to researchers at a fraction of the commercial cost.

“We’re sitting on a $250 million collection that’s nowhere else,” says Soll, who came to the UI in 1972. “We’re the largest non-commercial hybridoma bank in the world. And we’re the only national resource, of hundreds created by the NIH, that hasn’t taken a cent of institutional money.”

The bank houses more than 4,000 hybridomas. A hybridoma is formed when a B cell (which makes an antibody) is paired with a cancer cell. The hybridomas secrete monoclonal antibodies, and it’s these uniquely created agents that have galvanized the field of cancer research.

Here’s why: Antibodies can attach themselves to certain antigens (or proteins) on cells, including cancer cells, and stop them from growing or making tumors. If researchers can create an antibody that targets a single antigen, such as one linked to a particular cancer cell, then that antibody can be mass produced.

“Monoclonal antibodies are the ultimate cancer fighters,” Soll says. “They now represent approximately a quarter of all current cancer drugs and the majority under development.”

But cancer cells are devious and adaptable, capable of avoiding detection or reproducing so rapidly that the body’s natural defenses can’t keep up. In the past two decades, the U.S. Food and Drug Administration has approved about 35 monoclonal antibodies to treat certain cancers. However, most of the monoclonal antibodies so far identified haven’t worked well, which is why there’s still a concerted effort to discover new ones.

Soll’s mission to identify improved cancer-fighting monoclonal antibodies is personal: His wife died from brain cancer six years ago. He didn’t leave her bedside for four months. After her death, Soll switched his research focus to cancer and is working to create a monoclonal antibody that would stop cancer tumors from forming, no matter the type. The bank, with its supply of monoclonal antibodies, coupled with his lab’s novel 3-D imaging that tracks tumor formation and growth in real time, is “a serendipitous marriage of technologies” for his work, Soll says. “I know a potent anti-tumor antibody is out there,” Soll says. “If I find it, then I can look up to heaven and tell her I did something.”

The monoclonal antibodies also are used for a host of other basic applications in biology, such as identifying and studying proteins in human diseases. “They’re used for everything. They’re universal,” Soll says. “They’ll never become out of date.” The bank has some 60,000 active clients worldwide, and it sets the UI apart from other research institutions.

“The Developmental Studies Hybridoma Bank is one of the many ‘hidden’ treasures at the University of Iowa that are in plain sight, a national resource for one of the most important, exciting, and promising areas of research right now,” says Dan Reed, UI vice president for research and economic development.

The client list includes many UI scientists. One of them, Kevin Campbell, professor and head of the Department of Molecular Physiology and Biophysics, has worked with the bank since its inception. Campbell uses the hybridomas to identify the proteins present—or absent—in various forms of muscular dystrophy.

“It’s like a natural resource,” says Campbell, who has stored at least 10 ten of his lab’s monoclonal antibodies at the bank. “Most scientists know about the hybridoma bank and know it’s located at the University of Iowa.”

Adapted from news release by University of Iowa