The Gairdner Foundation has announced that 

, is one of the 2022 Canada Gairdner Award laureates for seminal discoveries and contributions to biomedical science.

Orkin, the David G. Nathan Distinguished Professor of Pediatrics at 

Dana-Farber/Boston Children’s Cancer and Blood Disorders Center

 and Harvard Medical School, and a Howard Hughes Medical Institute Investigator, was recognized for the discovery of the molecular mechanism responsible for the switch from fetal to adult hemoglobin gene expression during human development and translating that knowledge into a novel treatment for the hemoglobin disorders — sickle cell disease and beta-thalassemia.

The Gairdner Foundation was established in 1957 by Toronto stockbroker, James Gairdner to award annual prizes to scientists whose discoveries have had a major impact on scientific progress and on human health. Since 1959 when the first awards were granted, 402 scientists have received a Canada Gairdner Award, and 96 to date have gone on to receive the Nobel Prize. The Canada Gairdner Awards promote a stronger culture of research and innovation across the country through outreach programs including lectures and research symposia.

Orkin’s pioneering work in genetic disorders of hemoglobin spans four decades and has unraveled molecular mysteries behind how blood cells develop and how disorders of blood arise. His most recent studies led to the discovery of the molecular mechanism responsible for the switch from fetal (HbF) to adult (HbA) hemoglobin gene expression that occurs during human development. Capitalizing on genetic clues from human population studies, Orkin and colleagues established that the protein BCL11A acts as the critical silencer of HbF expression in adults. Recognizing that turning HbF expression back on could lessen disease severity of sickle cell disease and beta-thalassemia — genetic disorders affecting HbA production — he proposed downregulation of BCL11A as a therapeutic approach. Dialing down the amount of BCL11A would reactivate HbF expression and effectively substitute for mutant or deficient HbA in these disorders. His group first demonstrated that downregulation of BCL11A expression corrects sickle cell disease in engineered mice, an important proof-of-principle for therapeutic translation. He and colleagues identified a discrete site in a regulatory element within the BCL11A gene itself that, if deleted by CRISPR gene editing in blood stem cells, would impair BCL11A expression only within developing red blood cells, and safely reactivate HbF expression. This work laid the groundwork for highly promising, ongoing clinical trials in patients with sickle cell disease and beta-thalassemia, diseases that affect >5 million individuals worldwide. Reactivation of HbF in patients in these genetic therapy trials has yielded transformative results: freedom from sickle crises and anemia in sickle cell disease and transfusion-independence in beta-thalassemia.

His work has had a tremendous impact and much of what is known about the control of gene expression during blood cell development can be traced directly to Orkin’s pioneering studies. His discoveries have paved the way for clinical approaches that will revolutionize the treatment of hemoglobin disorders — sickle cell disease and beta-thalassemia — that affect more than five million people worldwide. Clinical trials that are currently underway establish the therapeutic potential of HbF reactivation. The outcomes of these trials will have significant impact for patients suffering from hemoglobin disorders around the globe and will encourage the future development of cheaper and more readily accessible therapies for global application.

More information about the other award winners is available at 

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The Gairdner Foundation has announced that Stuart H. Orkin, MD, is one of the 2022 Canada Gairdner Award laureates for seminal discoveries and contributions to biomedical science.

2022 Canada Gairdner Award Given to Stuart H. Orkin, MD, Researcher at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center

 is launching a year-long celebration of its 75th anniversary to highlight its history and progress in cancer care and transformative cancer research. In marking the notable anniversary, Dana-Farber seeks to recognize the Institute’s many scientific discoveries, advancements in cancer care for patients, and its extraordinary contributions to eradicating cancer in both children and adults.

“From the first remissions with chemotherapy in 1947 to the most recent new immunotherapies, Dana-Farber has helped push progress against cancer for patients, everywhere,” said Dana-Farber President and CEO, 

. “We celebrate the rich history this anniversary represents, even as we rededicate ourselves to relieve the burden of cancer in the years ahead.”

Dana-Farber will celebrate the milestone anniversary throughout 2022 with signage around the Longwood Medical Area, a dedicated web hub, social media content featuring historical moments in Dana-Farber history, a workforce celebration, and other events to be announced throughout the year. Other historical initiatives, include a 

 video project to capture thoughts and memories from key figures from Dana-Farber’s history.

Boston Mayor Michelle Wu will also issue a City of Boston Proclamation today, announcing March 30, 2022 as Dana-Farber Cancer Institute Day.

“Our work over many decades has been marked by an incredible community of scientists, clinicians, nurses, staff and volunteers, all working together with our patients and families for the best possible outcome today and tomorrow,” said Josh Bekenstein, chairman of the Board of Trustees. “We are grateful for their efforts and dedication to the mission we all share.”

In 1947, Sidney Farber, MD, founded the Children's Cancer Research Foundation, dedicated to providing compassionate, state-of-the-art treatment to children with cancer while developing the cancer preventatives, treatments, and cures of the future.

The foundation officially expanded its programs to include patients of all ages in 1969, and in 1974 became known as the Sidney Farber Cancer Center in honor of its founder. The long-term support of the Charles A. Dana Foundation was acknowledged by incorporating the Institute under its present name in 1983.

Throughout its history, Dana-Farber researchers and physicians have contributed numerous scientific breakthrough in both the understanding of cancer biology and the treatment of the disease across all types of cancer including:

1954: Farber and his colleagues achieve the first remissions of Wilms' tumor, a common form of childhood cancer, and boost cure rates from 40 percent to 85 percent.

1974: Drs. Emil Frei III and Stephen Sallan start the first in an ongoing series of clinical trials for children diagnosed with acute lymphoblastic leukemia (ALL). These trials dramatically improve treatment and play a key role in building toward today's cure rates of 85 to 90 percent.

1996: Institute researchers dramatically advance the understanding of how HIV, the virus that causes AIDS, replicates and infects healthy cells. Science magazine heralds this discovery as its "Breakthrough of the Year".

1998: A drug called imatinib (Gleevec), the early work for which was done at Dana-Farber, achieves striking success in many patients with chronic myelogenous leukemia.

2001: Dana-Farber researchers discover that many cancer cells carry a surface protein called PD-L1, which staves off an attack by immune system T cells. The discovery lays the foundation for immunotherapy drugs.

Over the last decade, Dana-Farber researchers have helped to usher in a new era in personalized cancer treatment using precision medicine, targeted treatments and becoming a world leader in leveraging the human immune system to fight cancer. Advancements have included:

Nivolumab (Optivo) becomes the first drug targeting the PD-L1 protein on cancer cells to be approved by the U.S. Food and Drug Administration. The drug, part of a revolution in cancer immunotherapy, derives from research by Dana-Farber scientists.

Officials launch Profile, a research program that enables all adult patients treated at the Dana-Farber Brigham Cancer Center to have their tumor tissue scanned for genetic mutations known or suspected of being linked to cancer.

A personal cancer treatment vaccine that targets distinctive "neoantigens" on tumor cells can stimulate a potent, safe, and precisely targeted anti-tumor response in patients with melanoma, scientists at Dana-Farber and the Broad Institute report.

Following a clinical trial led by Dana-Farber investigators, the 

U.S Food and Drug Administration grants its first approval for CAR T-cell therapy for adults with multiple myeloma.

William Kaelin Jr., MD, is named a co-recipient of the 2019 Nobel Prize in Physiology or Medicine

 for research into the mechanism by which cells sense and adjust to varying levels of oxygen.

Dana-Farber researchers have contributed to the development of 35 of 75 cancer drugs recently approved by the FDA for use in cancer patients.

The Institute is internationally renowned for its equal commitment to cutting edge research and provision of excellent patient care.

Dana-Farber Cancer Institute is a principal teaching affiliate of Harvard Medical School, a federally designated Center for AIDS Research, and a founding member of the Dana-Farber/Harvard Cancer Center, a federally designated comprehensive cancer center. Dana-Farber also maintains affiliations with several schools of nursing in the Boston area.

Dana-Farber is supported by the National Cancer Institute, the National Institute of Allergy and Infectious Diseases, and the generous support of numerous foundations and individuals who contribute to the Institute's individual research and clinic programs or to 

, the principal charity of the Institute, named for one of its child patients.

For more information on Dana-Farber’s 75th anniversary, visit 

Dana-Farber Cancer Institute is launching a year-long celebration of its 75th anniversary to highlight its history and progress in cancer care and transformative cancer research. 

Dana-Farber Cancer Institute Celebrates 75th Anniversary

A combination of two drugs that open the floodgates to an immune system attack on cancer curtailed tumor growth in some patients with non–small cell lung cancer (NSCLC) that was resistant to a single immunotherapy agent, results from a recent clinical trial show. The addition of radiation therapy to the two-drug regimen did not improve outcomes, however, researchers at Dana-Farber Brigham Cancer Center and other centers report in a new study.

, is part of a broad-based effort to extend the benefits of drugs known as immune checkpoint inhibitors by combining them with other treatments and with one another. The new trial is one of the first to test radiation therapy in combination with immune therapy in patients with cancer. The fact that radiation therapy didn’t enhance the effect of the two-drug therapy suggests that future studies should explore different combinations, the study authors say.

“Patients with NSCLC that doesn’t respond to checkpoint inhibitors known as PD(L)-1 inhibitors have few treatment options. In this trial, we tested a PD-L1 inhibitor in combination with a drug that targets a different immune checkpoint protein, CTLA-4 — an approach that has shown promise in laboratory research but hasn’t been extensively tested in patients whose NSCLC is resistant to PD(L)-1 inhibitors,” says study lead author 

“We not only found that the combination brought the cancer under control in some patients, but our laboratory work suggests a way of determining 

 patients are likely to have this benefit,” he remarked.

The trial is part of a wave of research into combinations of checkpoint inhibitors and other therapies in patients with cancer. The inhibitors work by stifling “checkpoint” proteins on cancer cells or immune system cells that would otherwise protect tumors from an immune system attack. Such drugs have proved highly effective against certain types of cancer, but they’ve been less successful, on their own, in many other types.

One promising solution has been to use checkpoint inhibitors in conjunction with radiation therapy. A phase 2 clinical trial of that combination in patients with metastatic NSCLC produced encouraging results, but it wasn’t clear what dose of radiation works best.

The new trial set out to answer that question in patients with NSCLC resistant to PD(L)-1 inhibitors, and to evaluate a combination of PD-L1 and CTLA-4 inhibitors, with and without radiation, in these patients.

The trial involved 78 patients at 18 cancer centers in the U.S. All participants received the drugs durvalumab (which targets the PD-L1 checkpoint protein on tumor cells) and tremelimumab (which targets CTLA-4). One-third of them were also treated with low-dose radiation therapy followed by durvalumab. And one-third were treated with higher-dose, “hypofractionated” radiation therapy followed by durvalumab.

There was no difference in response rates between patients treated with radiation therapy and those in the immunotherapy-only group, investigators found. At the same time, though, about 30% of the patients had their disease brought under control, including 10% who had long-lasting responses to treatment – an impressive outcome considering that all participants had cancers that were resistant to PD(L)-1 inhibitors.

As part of the study, researchers analyzed tumor tissue samples from the participants. They found that those whose tumors teemed with immune system T cells were more likely to respond to the treatment than those with fewer T cells in their tumor tissue.

“Our findings suggest that durvalumab/tremelimumab should be further explored for its ability to benefit NSCLC patients who have progressed on prior PD(L)-1 therapy,” Schoenfeld said. “In future trials of these and similar agents, analyzing tumor tissue for T-cell infiltration may be able to identify patients who can most benefit from this type of treatment.”

The senior authors of the paper are Catherine J. Wu, MD, and F. Stephen Hodi, MD, of Dana-Farber; Helen X. Chen, MD, of the National Cancer Institute; and Arta M. Monjazeb, MD, of the University of California Davis Comprehensive Cancer Center. Co-authors are: Anita Giobbie-Hurder, MS, Yang Liu, PhD, Aashna Jhaveri, MS, Lin Yang, MS, Jennifer Altreuter, MD, Jason L. Weirather, PhD, Srinika Ranasinghe, PhD, Katrina Z. Kao, Ana Lako, PhD, Ryan C. Brennick, Scott J. Rodig, MD, and Mark M. Awad, MD, of Dana-Farber; Lauren Gunasti and Raymond H. Mak, MD, of Dana-Farber Brigham Cancer Center; Junko Tsuji, PhD, Hayley Lyon, Carrie Cibuskis, and Niall Lennon, PhD, of the Broad Institute of MIT and Harvard; Ryan D Gentzler, MD, of the University of Virginia Cancer Center; Carrie Lee, MD, of the University of North Carolina Lineberger Comprehensive Cancer Center; Joleen Hubbard, MD, of the Mayo Clinic; Susanne M. Arnold, MD, of the University of Kentucky Markey Cancer Center; James L. Abbruzzese, MD, of Duke Cancer Institute; Salma K. Jabbour, MD, of Rutgers Cancer Institute of New Jersey; Nataliya V. Uboha, MD, of the University of Wisconsin Carbone Cancer Center; Kevin L. Stephans, MD, of the Cleveland Clinic; Jennifer M Johnson, MD, of Sidney Kimmel Cancer Center; Haeseong Park, MD, of Siteman Cancer Center, Washington University, St. Louis, Mo; Liza C. Villaruz, MD, of the University of Pittsburgh Medical Center Hillman Cancer Center; and Elad Sharon, MD, Howard Streicher, MD, and Mansoor M Ahmed, PhD, of the National Cancer Institute.

The study was funded by the National Institutes of Health and Dana-Farber, including grant UM1 CA186709, a Biomarker Supplement to UM1 CA186709. Funding also included grants U24CA224331 and U24CA224316.

A combination of two drugs that open the floodgates to an immune system attack on cancer curtailed tumor growth in some patients with non–small cell lung cancer that was resistant to a single immunotherapy agent.

Dana-Farber Cancer Institute

Articles

2022 Canada Gairdner Award Given to Stuart H. Orkin, MD, Researcher at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center

Dana-Farber Cancer Institute Celebrates 75th Anniversary

Immunotherapy Combination Shown to Benefit Some Patients with Non–Small Cell Lung Cancer Resistant to Single Immunotherapy