Hutch to serve as global hub for HIV vaccine and prevention: Two new international networks build on years of Hutch research on AIDS

Capping years of leadership in a multitude of HIV research projects, the Hutchinson Center will take center stage in two landmark, international HIV-vaccine and HIV-prevention projects.

Both funded by the National Institutes of Health, the HIV Vaccine Trials Network and the HIV Prevention Trials Network will dramatically expand international research on HIV, the cause of AIDS.

The HIV Vaccine Trials Network will provide a comprehensive, clinically based, worldwide network to develop and test preventive vaccines for the virus that has caused a global epidemic affecting an estimated 40 million people.

“This represents the development of a new global international clinical trials network to speed the development of an HIV vaccine,” says Dr. Larry Corey, head of the Hutch’s infectious diseases program and professor at the University of Washington.

Corey will direct the network’s core operations center, which will be located at the Hutch.

The Hutch also was selected as one of the network’s 10 clinical vaccine units, to be directed by Dr. Julie McElrath, an investigator in the Hutch’s Clinical Research Division. This unit is an extension of the AIDS Vaccine Evaluation Unit, also directed by McElrath, which was established at the Hutch and UW in the 1980s.

In addition, the Hutch will serve as home to the network’s statistical and data management center led by the Hutch’s Dr. Steve Self.

“A very large number of collaborators who haven’t been involved before will join this project,” Corey said. “There will be more people, laboratories and sites involved in a more cohesive effort than ever before.”

The new network increases opportunities for scientific creativity by fostering collaboration among industry, academia and government and also provides a significant amount of funding. First-year costs for the project are $29 million.

At the 13th International AIDS Conference in July in Durban, South Africa, NIH announced the formation of the HIV Prevention Trials Network, a $30 million international organization to study non-vaccine prevention strategies for HIV.

The Hutchinson Center will receive $5 million to house the network’s statistical and data coordinating center, under the direction of the Hutch’s Dr. Thomas Fleming, who is also a faculty member of UW.

“A myriad of prevention strategies will be investigated,” Fleming says. “This is a great opportunity for those of us involved to develop new effective and deliverable preventions where the need is the greatest.”

The new network will constitute NIH’s largest comprehensive, multicenter network dedicated to non-vaccine prevention strategies, with research sites in Africa, Asia, Europe, South America and the United States.

“Developing countries are experiencing a severe health-care crisis,” Fleming says. “In some countries, one third of all pregnant women are infected with HIV, and more than 10 percent of infants are born with HIV infection.”

Prevention strategies aimed at developing countries where the AIDS crisis is epidemic will have impacts on the rest of the world.

“It’s naďve to think that it only affects those countries,” Fleming says. “An entire work force of young people is being wiped out by the disease, with enormous economic and political impacts.”

Although such impacts are of tremendous importance, Fleming notes that compassion is main motivation.

“Ultimately, it’s the humanitarian effort driving this,” he says.

Promise for adult leukemia: First antibody-targeted chemotherapy induces remission

The first antibody- targeted chemotherapy trials induced remission in a sizable number of adult patients with advanced leukemia, according to study data presented by the Hutchinson Center’s Dr. Eric Sievers.

The drug used for the trials—Mylotarg (also known as CMA-676)—was recently approved by the U.S. Food and Drug Administration to fight relapsed acute myeloid leukemia for some patients age 60 and older.

Because standard chemotherapy drugs to treat AML are non-specific, destroying normal as well as malignant cells, patients who receive the therapy tend to become very sick. With antibody-targeted chemotherapy, the drugs are delivered directly to the leukemia cells, sparing healthy cells.

“Mylotarg is a new option for many adult patients with AML,” says Sievers, of the Clinical Research Division. “Patients greater than 60 years of age achieved remission at a comparable rate to younger patients.”

Agent may prevent transplant reactions, boost tolerance

Hutchinson Center researchers have discovered a new treatment that may reduce or prevent graft-vs.-host disease, a major complication following bone-marrow transplants.

By controlling the activation of specific T cells by blocking the anti-CD28 antibody in mice, the researchers reduced or prevented graft-vs.-host disease.

While often there is a lot to be understood when moving from a mouse model to humans, Dr. Claudio Anasetti, lead researcher on the study, says the new information may lead to safer and more effective transplants. The next step, he says, will be human trials.

For patients this development could mean an easier recovery after marrow transplantation While long-term survival after marrow transplantation has increased significantly over the years and many people survive to live healthy and productive lives, some have difficult recoveries, and in some cases chronic conditions or death, resulting from graft-vs.-host disease.

Combined hormone-replacement therapy may boost incidence of rare form of breast cancer

The incidence of an uncommon form of breast cancer—lobular carcinoma—is on the rise in postmenopausal women nationwide, an increase that may be associated with the widespread use of combined hormone-replacement therapy, say Hutchinson Center researchers.

Lobular breast cancer, which involves the lobules—chambers in the breast that contain small milk-producing glands—accounts for only 5 to 10 percent of all invasive breast-cancer cases.

In one study, Dr. Christopher Li and colleagues at the Hutch reported a 2.6-fold increase in the incidence of lobular breast cancer among postmenopausal women who took combined hormone-replacement therapy for six months or more, as compared to those who took no hormones. This study involved nearly 1,000 Seattle-area women—half with breast cancer, half without.

In another study, Li and researchers from the Hutch and University of Washington reported a 70 percent increase in lobular breast cancer among postmenopausal women nationwide. For this study, the researchers looked at data from the Surveillance, Epidemiology and End Results program, or SEER, a national cancer registry operated by the National Cancer Institute.

“Although preliminary, our studies suggest that the incidence of lobular breast cancer is increasing nationwide and that the use of postmenopausal hormone-replacement therapy, specifically the use of combined estrogen plus progestin preparations, may be contributing to this increase,” Li says. “However, future studies are required to confirm these findings, and it is important to note that lobular tumors represent only 5 to 10 percent of all breast carcinomas.”

Genomics expert Trask to head Hutch’s Human Biology Division

Dr. Barbara Trask, an expert on genome organization and a leader in developing techniques for visualizing chromosomes in cells, will join the Hutchinson Center Oct. 1 as head of the Human Biology Division.

Trask is a professor and acting chair in the molecular biotechnology department at the University of Washington, where she has been on the faculty since 1992.

“She’s a terrific scientist working in the area of genomics and particularly localization of genes to chromosomes, so she’ll strengthen our genomics capabilities,” says Dr. Lee Hartwell, Hutchinson Center president and director.

“She has great, well-respected leadership skills, both in her national presence in the genome community and in a variety of roles she’s played at the university.”

Trask’s laboratory develops and utilizes techniques for visualizing chromosomes, including fluorescence in situ hybridization (FISH), in which segments of DNA are marked by fluorescent molecules. The technique allows researchers to pinpoint the location of specific genes or chromosomal regions within the cell’s nucleus.

The method, which reveals strikingly vivid, brightly colored images of chromosomes, is useful not only for identifying a gene’s “address” but also for detecting chromosomal rearrangements or abnormalities.

Hartwell says Trask’s arrival will be a strong addition to the Human Biology Division, which has been led by acting division director Dr. Michael Emerman since the spring of 1999.

Your Gifts at Work

Private donations started Kemp’s studies on tumor development

Without donations from people like you, the Hutchinson Center’s work to advance knowledge and save lives would not be possible. Your gifts fund preliminary studies that lead to grants for in-depth research. Here’s an example of your dollars at work.

Arriving at the Hutchinson Center in 1995, Dr. Chris Kemp was determined to develop model systems for understanding genes that contribute to cancer development. Using startup funds largely provided by private donations, Kemp and colleagues determined that a protein called p27 represents a new class of tumor-suppressor proteins.

When these proteins are low, tumors may form. Levels of p27 are abnormally low in a variety of human cancers, including those of the breast, prostate and ovary. The protein is currently one of the most promising prognostic markers for staging cancer progression.

Kemp’s initial breakthrough on p27, made possible by charitable donations, helped him secure more than $600,000 of funding from the American Cancer Society to continue work on the role of tumor suppressors in cancer development.