Donald W. Kufe, MD
Distinguished Physician, Dana-Farber
Professor of Medicine, Harvard Medical School
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Combination of Hypomethylating Agent, Venetoclax, and Personalized DC/Tumor Fusion Vaccine to Treat Acute Myelogenous Leukemia
Project Overview
- Acute Myeloid Leukemia (AML) is a lethal hematological cancer for which chemotherapy is inadequate and rarely curative
- A current standard of care therapy for AML is a hypomethylation agent (HMA) (i.e., decitabine), together with venetoclax, a Bcl-2 inhibitor, which is a combination therapy that is well tolerated in elderly subjects. However, less than 40% of the subjects achieve complete remission, highlighting the need for additional therapeutic interventions for the prevention and treatment of cancers such as AML.
- Scientists have created a dendritic cell-based tumor vaccine to be combined with HMAs and venetoclax for treating AML.
- The technology is available for licensing.
Technology
Acute Myeloid Leukemia (AML) is a lethal hematological cancer for which chemotherapy is inadequate and rarely curative. Elderly AML patients tend to respond to standard therapies at lower rates relative to their younger counterparts, with approximately 60% of elderly subjects undergoing therapy suffering a recurrence, while >85% of subjects develop primary resistance and relapse after induction therapy.
A promising cancer treatment strategy is dendritic cell (DC)-based tumor vaccines, as DCs are capable of stimulating primary immune responses.
Researchers at Dana-Farber and Beth Israel Deaconess Medical Center, have leveraged this technique by fusing patient-derived tumor cells with autologous DCs as a combination therapy along with venetoclax and HMA. This invention is based on the discovery that DC-tumor fusion vaccines are able to rescue the deleterious immunomodulatory effects that are common with Bcl-2 inhibitors, either alone or in combination with HMAs.
This combination therapy has demonstrated efficacy in vitro and in vivo. In vitro, it resulted in enhanced expansion of CD4+ and CD8+ T cells expressing IFNg, increased T cell activation, and enhanced expansion of antigen-specific T cells. In vivo, mice challenged with the murine TIB-49 AML cell line showed better survival than those treated with vaccination alone, or venetoclax and HMA combined.
Team Members: Donald W. Kufe, MD, David Avigan, MD, Jacalyn Rosenblatt, MD, Dina Stroopinsky, PhD
Applications
- Combining DC-tumor fusion vaccine with a standard of care AML therapy (venetoclax/HMA) to treat a variety of hematologic cancer, such as AML and multiple myeloma, and solid cancers.
- Additional applications of this therapeutic approach may include also administering an immune checkpoint inhibitor or an immunomodulatory agent, such as lenalidomide, as part of the combination therapy.
Opportunities
Dana-Farber is looking for the right partner with an interest in licensing these assets for further development into new oncology therapeutics.
Team Members
David Avigan, MD
Cancer Center Director, Beth Israel Deaconess Medical Center (BIDMC)
Beth Israel Lahey Health Chief, Division of Hematology and Hematologic Malignancies, BIDMC
Professor of Medicine, Harvard Medical School
Jacalyn Rosenblatt, MD
Associate Chief, Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center
Associate Professor of Medicine, Harvard Medical School
Dina Stroopinsky, PhD
Former Translational Scientist, Beth Israel Deaconess Medical Center
