BOSTON – A personalized cancer vaccine markedly improved outcomes for patients suffering from acute myeloid leukemia (AML), a potentially lethal blood cancer, in a clinical trial led by investigators at Beth Israel Deaconess Medical Center (BIDMC). The product of a long-term collaboration among investigators at the Cancer Center at BIDMC and Dana-Farber Cancer Institute, the vaccine stimulated powerful immune responses against AML cells and resulted in protection from relapse in a majority of patients, the team of researchers reported today in Science Translational Medicine.
"Immunotherapy strategies leverage the body's own defense systems to fight cancer cells," said senior author David Avigan, MD, Chief, Section of Hematological Malignancies and Director of the Cancer Vaccine Program at the BIDMC Cancer Center and Professor of Medicine at Harvard Medical School. "By creating a personalized vaccine, we use the power of the immune system to selectively target each patient's cancer and avoid the side effects of chemotherapy."
Patients with AML may achieve remission following standard chemotherapy, yet relapse is common, and most patients ultimately succumb to the disease. In this study, the team of collaborators from BIDMC and Dana-Farber generated personalized vaccines for 17 patients with AML who were in remission after undergoing standard chemotherapy.
Despite an average age of 63, more than 70 percent of trial participants remained in remission at an average follow-up period of more than four years. After receiving a series of injections of the vaccine, patients demonstrated an increase in the number of leukemia-specific T cells in the blood and bone marrow. T cells are immune cells critical to the body's ability to recognize and remember pathogens like viruses, or in this case, cancer cells. Present only in low numbers prior to vaccination, T cells recognizing AML cells were expanded after vaccination, potentially providing long-term protection against the leukemia.
"With the vaccine, we use the immune system to target the whole tumor including cells that may be resistant to chemotherapy," stated lead author Jacalyn Rosenblatt, MD, Co-Director of the Cancer Vaccine Program at the BIDMC Cancer Center and Assistant Professor of Medicine at Harvard Medical School. "We were really excited to see that the vaccine generated a broad and durable immune response without significant side effects."
This vaccine platform has been the product of collaboration among BIDMC and Dana-Farber investigators, including the initial seminal work done by Donald W. Kufe, MD, Distinguished Physician at Dana-Farber, subsequent development and clinical translation by Kufe, Rosenblatt and Avigan, and the contributions of clinical investigators including Richard Stone, MD, Chief of the Adult Leukemia Program at Dana-Farber, and Lynne Uhl, MD, Director of Transfusion Medicine at BIDMC.
"The development of this personalized vaccine by our team was based on the premise that effective treatment of established cancers would require the induction of immunity against multiple antigens, including neoantigens, specifically expressed by the patient's own cancer cells," stated co-author Donald W. Kufe, MD.
Based on these encouraging results, researchers are also testing this vaccine approach in other types of cancers.
Avigan and colleagues are leading a national study to test the effectiveness of the vaccine in patients with multiple myeloma, another common blood cancer. Conducted under the auspices of the NIH-sponsored Clinical Trials Network, this first-of-its-kind endeavor brings together 15 leading cancer centers. Of note, the unique research effort takes an open-source approach, in which participating sites were trained in vaccine production at BIDMC and will work together to bring this therapy to patients nationwide.
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Study coauthors also include Lynne Uhl, MD; Robin Joyce, MD; James D. Levine, MD; Jon Arnason, MD; Malgorzata McMasters, MD; Katarina Luptakova, MD; Salvia Jain, MD; Jeffrey I Zwicker, MD; Ayad Hamdan, MD; Vassiliki Boussiotis, MD, PhD; Poorvi Somaiya Dutt, MS; Emma Logan, BSN; Mary Paty Bryant; Dina Stroopinsky, PhD; Kristen Palmer, MA; Max Coll; Abigail Washington; and Leandra Cole, all of BIDMC. Co-authors also include Richard M. Stone, MD; David P. Steensma, MD; Daniel J. deAngelo, MD, PhD; and Ilene Galinsky, MSN, all of Dana-Farber.
This work was supported by grants from the National Institutes of Health/National Cancer Institute (NIH/NCI R21CA149987-02) and from the Leukemia and Lymphoma Society Translational Research Program. Additional support for early vaccine work was provided by the Louis B. Mayer Foundation, and the Barbara and James Sadowsky Fund.
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Story Source: Materials provided by Scienmag
