Adam D Cohen, MD
Fox Chase Programs
1. Developmental therapeutics for multiple myeloma and amyloidosis
Multiple myeloma is a cancer of the bone marrow affecting 20,000 new U.S. patients each year, in which proliferation of malignant bone marrow plasma cells leads to bone lesions, kidney damage, anemia, and recurrent infections. Systemic light-chain (AL) amyloidosis is a rare, related plasma cell disorder in which a toxic misfolded protein is deposited into organs such as heart, kidney, and liver, leading to eventual organ dysfunction and failure. Novel drugs such as thalidomide, lenalidomide, and bortezomib, as well as advances in hematopoietic stem cell transplantation, have significantly improved outcomes for myeloma and amyloidosis patients in the past decade, but both diseases remain largely incurable, and new approaches to treatment continue to be needed.
Fortunately, scientific advances in the underlying pathophysiology of these diseases have led to a number of new targets for therapeutic development. Our program is dedicated to the evaluation of promising new agents in early-stage clinical trials, both for newly-diagnosed and relapsed/refractory patients. Such trials advance our understanding of how best to treat these difficult diseases, and importantly offer patients access to agents that may not yet be available, often providing additional options when standard therapeutic approaches have been exhausted. Our current protocols are studying molecularly-targeted inhibitors of kinesin spindle protein and NEDD8-activating enzyme, which are involved in myeloma cell cycle progression and protein degradation pathways, respectively, as well as monoclonal antibodies against BAFF or IL-6, two signaling molecules which promote myeloma cell proliferation and survival. Planned studies for 2011 include evaluation of new proteasome inhibitors for myeloma and amyloidosis, as well as trials involving novel immunomodulatory drugs, monoclonal antibodies, and vaccines. We also continue to collaborate with the Temple/Fox Chase Bone Marrow Transplant program to explore ways to improve autologous stem cell transplantation as a treatment modality for these diseases.Top
2. Modulation of anti-tumor immunity in lymphoid malignancies
A growing body of literature has demonstrated that the clinical behavior of certain cancers, including lymphoid malignancies like multiple myeloma and lymphoma, is determined not only by the intrinsic biology of the malignant cells, but also by the ability of the host immune system to recognize and respond to these cells. Our pre-clinical/translational research program is dedicated to gaining greater understanding of immune cell function in lymphoid malignancy patients, as well as exploring therapeutic approaches to augment immune responses against these diseases. In collaboration with Kerry Campbell, Ph.D., we are using multi-parameter flow cytometry and ex vivo functional assays to extensively characterize immune cell phenotype and function in lymphoid malignancy patients, with a particular focus on natural killer (NK) cell activity and how these cells are affected by currently-used therapies. From a therapeutic perspective, we are interested in a novel class of antibodies that enhance T or NK cell-mediated anti-tumor immunity via modulation of signaling through receptors expressed on their surface, such as GITR (glucocorticoid-induced TNF receptor), CD137/4-1BB, or the KIR (killer-cell immunoglobulin-like receptor) family. We also are exploring therapeutic vaccine approaches to stimulate anti-tumor immunity, with a pilot clinical trial using a recombinant MAGE-A3 protein vaccine currently in development for multiple myeloma patients.Top