Lenalidomide in Combination with Dendritic Cell (DC) / Tumor Cell Fusion Vaccine Enhances Immune Response

Project Overview

• Lenalidomide is a medication that has achieved success in the treatment of both inflammatory disorders and various cancers. In vitro, lenalidomide exerts direct anti-tumor effects, inhibition of angiogenesis, and possesses immunomodulatory roles, whereas in vivo, its effects include immunomodulatory activities, the induction of tumor cell apoptosis, and antiangiogenic and anti-osteoclastogenic effects.
• A promising cancer treatment strategy is dendritic cell (DC)-based tumor vaccines due to the ability of DCs to stimulate primary immune responses.
• Dr. Donald Kufe’s lab at Dana-Farber has developed a method fusing patient-derived myeloma cells with autologous DCs to successfully induce cellular and humoral immune responses leading to disease stabilization. Hence, the success of lenalidomide and DC-based tumor vaccines can be leveraged to treat many hematologic and solid cancers. 
• This fusion vaccine technology is seeking to license this technology.

Technology

The fusion vaccine invention relates to a method for cancer treatment involving the administration of autologous DC/tumor fusions in combination with lenalidomide as an immunomodulatory agent. This method is applicable to either solid tumors, such as breast or renal tumors, or hematologic malignancies, including acute myeloid leukemia (AML) or multiple myeloma (MM).

This invention may additionally include administering a checkpoint inhibitor one week after the DC/tumor fusions, including PD1, PDL1, PDL2, TIM3, or LAG3 inhibitors and PD1, PDL1, TIM3, or LAG3 antibodies. Other variations of the method may involve further administering an agent that targets regulatory T cells or administering Toll-like receptor (TLR) agonists.

This combination therapy shows promise by enhancing vaccine response as demonstrated by the expansion of IFN-producing cells, decreased expansion of regulatory T cells and inhibitory cytokines, as well as increased T cell-mediated killing of myeloma targets. This technology lays the basis for DC/tumor fusion combination therapy in conjunction with lenalidomide and demonstrates improved efficacy relative to each treatment independently. 

Further Details: 

Luptakova, K., Rosenblatt, J., Glotzbecker, B. et al. Lenalidomide Enhances Anti-Myeloma Cellular ImmunityCancer Immunol Immunother 62, 39-49 (2013).

Team Members: Donald W. Kufe, MD, David Avigan, MD, Jacalyn Rosenblatt, MD

Applications

Combination vaccine and immunomodulatory therapy as cancer immunotherapy to treat a variety of hematologic and solid cancers. 

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

Donald W. Kufe, MD

Distinguished Physician, Dana-Farber

Professor of Medicine, Harvard Medical School

Donald's Bio

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

David's Bio

Jacalyn Rosenblatt, MD

Associate Chief, Division of Hematology and Hematologic Malignancies, Beth Israel Deaconess Medical Center

Associate Professor of Medicine, Harvard Medical School

Jacalyn's Bio