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Promising results in trial of engineered T cells in high-risk leukemia

High response rates to experimental immunotherapy in patients with treatment-resistant chronic lymphocytic leukemia

Dec. 3, 2016 | By Susan Keown / Fred Hutch News Service

Dr. Cameron Turtle

Dr. Cameron Turtle presented findings regarding CAR T-cell therapies in leukemia and lymphoma patients at the annual meeting of the American Society of Clinical Oncology last June in Chicago.

ASCO file photo

The 24 patients had undergone most standard therapies available to them and yet their chronic lymphocytic leukemia had come back strong. Almost all of them had been treated with a newly approved, targeted drug called ibrutinib; data from other studies show that most patients whose disease progresses after ibrutinib treatment do not survive long. The majority of the 24 had chromosomal markers in their leukemia cells that serve as[DAE1]  “predictors of a bad response to most standard therapies,” said Dr. Cameron Turtle of Fred Hutchinson Cancer Research Center.

But most of these patients, who were enrolled in a small, early-phase trial, saw their advanced tumors shrink or even disappear after an infusion of genetically engineered immune cells. Turtle, one of the study’s leaders, presented the results on Saturday at the 2016 annual meeting of the American Society of Hematology in San Diego.

In the trial, participants’ disease-fighting T cells were removed from their blood and genetically engineered in a lab at Fred Hutch to produce an artificial receptor, called a CAR, or chimeric antigen receptor, that empowered them to recognize and destroy cancer cells bearing a target molecule called CD19. After patients received chemotherapy, the CAR T cells were infused back into their bloodstream to kill their CD19-positive cancers.

While all 24 patients with chronic lymphocytic leukemia, or CLL, received the experimental therapy, Turtle focused in his presentation on the results in a subgroup of 19 patients who received particular chemotherapy regimens and doses of CAR T cells the researchers now prefer, based on recent data in other groups of patients on the trial.

Fourteen of 19 experienced a partial or complete regression of their disease in their lymph nodes. And of the 17 who had leukemia in their bone marrow when they enrolled on the trial, the marrow became cancer-free in 15 after they received CAR T cells. (In his presentation, Turtle presented new results not reflected in the abstract available online.)

“It’s very pleasing to see patients with refractory disease respond like this,” Turtle said. The research team “had seen very good responses [to the same CAR T-cell therapy] in acute lymphoblastic leukemia and non-Hodgkin lymphoma, so we hoped responses would be good in CLL too.”

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In Uganda, strengthening a partnership against cancer

A ‘compelling and inspiring visit’ yields renewed commitment by Fred Hutch, Ugandan leaders

Dec. 2, 2016 | By Mary Engel / Fred Hutch News Service

Fred Hutch's Dr. Gary Gilliland and UCI's Dr. Carol Nakisige

Fred Hutch President and Director Dr. Gary Gilliland and Dr. Carol Nakisige, a UCI gynaecologist and obstetrician, confer at the UCI-Fred Hutch Cancer Centre in Kampala, Uganda, in November.

Photo by Jiro Ose / for Fred Hutch News Service

Uganda will increase funding to its public cancer institute by 25 percent after government officials met in the capital, Kampala, with Uganda Cancer Institute Director Dr. Jackson Orem and Fred Hutchinson Cancer Research Center President and Director Dr. Gary Gilliland and Senior Vice President Dr. Julie McElrath.

Fred Hutch has partnered with the UCI for more than a decade. What began as a small research collaboration has grown to include training and outpatient clinical care in a new, 25,000-square-foot UCI-Fred Hutch Cancer Centre, which opened in May 2015.

It was Gilliland’s first visit to the site, which he described in a meeting Thursday back in Seattle with Fred Hutch’s Global Oncology staff as a “state-of-the-art facility as good as anything we have here” in the United States.

Dr. Charles Babutunga, Leticia Nakayenga and Brenda Nakimera

The UCI's Dr. Charles Babutunga examines Brenda Nakimera, 9, as her mother Leticia Nakayenga looks on at the UCI-Fred Hutch Cancer Centre.

Photo by Jiro Ose / for Fred Hutch News Service

But Gilliland reserved his highest praise for the alliance’s Ugandan physicians, nurses and other clinicians he met, many of whom have trained in Seattle or in alliance programs in Kampala.

“To see the dedication and devotion of healthcare professionals in caring for those patients under difficult conditions was compelling and inspiring,” he said. “It was a stark reminder of how important it is to try to have an impact.”

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'She made me excited about science'

Dr. Julie Overbaugh is renowned both for her HIV research and thoughtful mentorship

Dec. 2, 2016 | By Sabrina Richards / Fred Hutch News Service

Dr. Julie Overbaugh

Dr. Julie Overbaugh

Photo by Robert Hood / Fred Hutch News Service

The young man in Mombasa, Kenya, was just 17 or 18 when Dr. Julie Overbaugh sat down to give him some insights into what she does so well: HIV research.

“I asked him about himself,” Overbaugh recalled. “And he said, ‘I’m the only one in my family left. My mom and my dad and my brothers and sisters are all dead from HIV.’

“What was inspiring was he said, ‘I want to do something. I want to do something with my life and I want to know how people do that’ … [Even through his loss] he wanted to be thinking about his future.”

Overbaugh, a scientist at Fred Hutchinson Cancer Research Center, is no stranger to the desire to help others. On hiatus from a Ph.D. in chemistry in Colorado, she spent four months in Oklahoma in 1982 aiding the effort to ratify the Equal Rights Amendment. And for more than 20 years, much of her HIV research has focused on people particularly vulnerable to HIV and its effects: commercial sex workers, and HIV-positive mothers and their infants in Kenya.

“She was one of the first basic scientists to join hands with clinical scientists, especially internationally, and have the foresight to see where we should be doing the research,” said Dr. Dara Lehman, a senior staff scientist in Overbaugh’s lab who also did her graduate work with her.

Overbaugh has contributed many insights into HIV transmission, the immune responses it triggers and those it evades, as well as its methods of slipping past our defenses, but it’s the relationships with people — family, colleagues, students and friends — of which she is most proud.

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Good News at Fred Hutch

Celebrating faculty and staff achievements

Dec. 1, 2016

Dr. Julie Overbaugh

Dr. Julie Overbaugh reacts to applause from friends and colleagues after winning the Nature Award for Mentoring in Science.

Photo by Robert Hood / Fred Hutch News Service

Dr. Julie Overbaugh recognized for lifetime of mentorship

Dr. Julie Overbaugh, an HIV researcher at Fred Hutchinson Cancer Research Center, was honored Thursday with the lifetime Nature Award for Mentoring in Science and a $10,000 prize. 

Nature, an international weekly journal of science, hosts these annual awards to champion those who inspire science’s next generation. This was the first year that the Nature Mentoring Awards, now in their 11th year, took place in the U.S. 

"Nobody who knows Julie — especially those who have known her as a mentor — are at all surprised that she was chosen,” said Fred Hutch President and Director Dr. Gary Gilliland. “To me, Julie epitomizes a central tenet of the Hutch — incredible science performed with the interest of others in mind.”

Overbaugh has contributed many insights into HIV transmission, the immune responses it triggers and those it evades, as well as its methods of slipping past immune defenses. In particular, she discovered a transmission bottleneck that limits the number and type of HIV variants that pass from one host to another, and she determined that sugar groups on the outside of HIV help shield the virus from protective antibodies.

Her work in maternal and infant HIV transmission helped elucidate the HIV transmission risk posed by breastfeeding, and it highlighted unique characteristics of the infant immune response that could inform vaccine development.

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On World AIDS Day, renewed hope for an HIV vaccine

Clinical trial taking place in South Africa could 'dramatically alter the course of the pandemic’

Dec. 1, 2016 | By Mary Engel / Fred Hutch News Service

Leading the HIV vaccine trial are a quartet of top physician-scientists from South Africa: Drs. Fatima Laher, Linda-Gail Bekker, Mookho Malahleha and Glenda Gray.

Fred Hutch file photo

World’s AIDS Day 2016 brings especially hopeful news: A large-scale clinical trial has opened in South Africa to test an experimental HIV vaccine regimen that could lead to the first licensed vaccine against the virus that causes AIDS.

The experimental vaccine under study is a modified version of the so-called Thai vaccine, which in 2009 became the only vaccine tested so far to show even modest protection against the rapidly mutating virus that has killed 35 million people worldwide since the HIV/AIDS pandemic began in 1981.

The new trial, called HVTN 702,  is funded by the National Institute of Allergy and Infectious Diseases, or NIAID, the Bill & Melinda Gates Foundation and the South African Medical Research Council and conducted by the NIAID-funded HIV Vaccine Trials Network, or HVTN, a global network headquartered at Fred Hutchinson Cancer Research Center.

“The people of South Africa are making history by conducting and participating in the first HIV vaccine efficacy study to build on the results of the Thai trail,” said trial chair Dr. Glenda Gray, president and executive officer of the South African Medical Research Council, in a statement released by NIAID. “If an HIV vaccine were found to work in South Africa, it could dramatically alter the course of the pandemic.” 

Gray is an HVTN co-director and head of its Africa programs. Co-chairing the trial with her are South African scientists Dr. Linda-Gail Bekker, deputy director of the Desmond Tutu HIV Centre at the University of Cape Town and chief operating officer of the Desmond Tutu HIV Foundation; Dr.  Fatima Laher, a director of the Perinatal HIV Research Unit at Chris Hani Baragwanath Hospital in Soweto; and Dr. Mookho Malahleha, deputy director of Setshaba Research Centre in Soshanguve.

It seems especially fitting that the four scientists leading the trial are women from Africa.  Globally, women make up half of the 36.7 million people living with HIV, and 80 percent of infected women live in sub-Saharan Africa, the region hardest hit by the pandemic. Most infections in sub-Saharan Africa are transmitted heterosexually. For biological, socioeconomic and cultural reasons, women are more vulnerable than men to acquiring HIV during sex.

In a culture in which men dominate relationships, women often can’t negotiate safer sex practices such as condom use or taking a daily antiretroviral pill known as PrEP to prevent infection. One of the appeals of a vaccine is that it can be used discretely, without a woman’s partner even knowing. 

“An HIV vaccine is the ultimate female prevention tool,” Gray said at a press conference at the recent international AIDS 2016 conference in Durban, South Africa. “You put it in your arm and it works in your vagina."

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A career of connections

New top hire Dr. Nancy Davidson will continue to build bridges as scientist, physician and leader at Fred Hutch, SCCA, UW

Dec. 1, 2016 | By Susan Keown / Fred Hutch News Service

Dr. Nancy Davidson

Dr. Nancy Davidson

Photo by Robert Hood / Fred Hutch News Service

For Dr. Nancy Davidson, the spark that ignited a career was, at first, just a summer job.

Then a med student, Davidson had sought a research job at the National Cancer Institute near her parents’ home to explore her interest in cancer ― and to supplement her lean student’s bank account.

But she found something there that “captured her imagination,” she recalled ― new cell models of breast cancer that created a tangible link between lab and clinic, allowing researchers to develop potential new treatments in Petri dishes that could then be brought to patients.

“This was at a time when we could begin to see the relationship between biology that was being studied in the laboratory and how it was going to ultimately translate into care for people,” she said.  

The passion for lab work that can directly impact patients’ lives has not left Davidson in the years since. The breast medical oncologist and researcher has built a worldwide reputation for her expertise and leadership in this field, for her work teasing out the role of hormones in breast cancer growth and her impact on the development of new standards of care that exploit the Achilles’ heels of breast cancer cells. 

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