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 Harvard Medical School and Beth Israel Deaconess Medical Center. The product of a long-term collaboration among investigators at the Cancer Center at Beth Israel Deaconess 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 inScience Translational Medicine.
“Immunotherapy strategies leverage the body’s own defense systems to fight cancer cells,” said senior author David Avigan, HMS professor of medicine, chief of the Hematological Malignancies/Bone Marrow Transplantation Program and director of the Cancer Vaccine Program at the Beth Israel Deaconess Cancer Center. “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 Beth Israel Deaconess 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, HMS associate professor of medicine and co-director of the Cancer Vaccine Program at the Beth Israel Deaconess Cancer Center. “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 Beth Israel Deaconess and Dana-Farber investigators, including the initial seminal work done by Donald Kufe, HMS professor of medicine at Dana-Farber, subsequent development and clinical translation by Kufe, Rosenblatt and Avigan, and the contributions of clinical investigators including Richard Stone, HMS professor of medicine and program director of the Adult Leukemia Program at Dana-Farber, and Lynne Uhl, HMS associate professor of pathology and director of the Division of Laboratory and Transfusion Medicine at Beth Israel Deaconess.
“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 Kufe.
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 Beth Israel Deaconess and will work together to bring this therapy to patients nationwide.