Nikhil C. Munshi, MD
Professor of Medicine, Harvard Medical School
Office phone: 617-632-4218
Preferred contact method: appointment phone
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Area of ResearchImmunotherapy and Molecular Manipulation in Multiple Myeloma
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA 02215
Dr. Munshi received his MD from Maharaja Sayjirao University, India, in 1984. He completed his postgraduate training in Internal Medicine at SSG Hospital and Maharaja Sayjirao University, followed by fellowships at Johns Hopkins Oncology Center and Indiana University Medical Center. In 2001, he joined Dana-Farber Cancer Institute and is currently the Associate Director of the Jerome Lipper Myeloma Center.
ResearchImmunotherapy and Molecular Manipulation in Multiple Myeloma
A major focus of our laboratory research has been identifying novel targets and antigens associated with multiple myeloma, and developing molecular therapeutic strategies including immunotherapy and immuno-gene therapy.
In an effort to define the ideal time for vaccination, we discovered both a decreased number and decreased activity of T regulatory cells in myeloma. We identified the cytokines produced in the bone marrow microenvironment that are responsible for this T regulatory cell dysfunction, making these cytokines an important target for improving T cell homeostasis. Moreover, based on our observation of the costimulatory effects of Revlimid (lenalidomide) through the B7-CD28 pathway, we are also developing therapeutic strategies using this agent, to improve immune responses.
Based on our in vitro results, we are developing clinical trials to evaluate vaccine strategies in myeloma. In particular, we studied the idiotype as a myeloma-specific antigen and observed specific immune responses. However, because therapeutic strategies directed against a single tumor-associated target may lead to immunological escape, we are identifying additional novel antigens with demonstrated in vivo immunogenicity in myeloma using pre- and post-vaccination patient serum and the Serological Analysis of Recombinant cDNA Expression Library (SEREX). For this work, we have cloned a series of molecules to form a panel of antigens for effective peptide- and protein-based vaccination in myeloma.
Another area of research in our laboratory is the evaluation of telomerase as a therapeutic target in myeloma. We identified molecular inhibitors of telomerase that are able to induce telomere shortening and eventual apoptotic cell death. In addition, we developed a unique murine model of human myeloma in which myeloma cells grow exclusively in a human bone implanted in the mice; we use this model to evaluate telomerase inhibitors for a clinical study.
The long-term goal of our research efforts is to develop novel therapeutic approaches to myeloma based on bench-side research and then to evaluate patient responses to find better avenues to effective therapy.
- LeBlanc R, Hideshima T, Catley S, Shringarpure R, Burger R, Mitsiades N, Mitsiades C, Cheema P, Chauhan D, Richardson P, Anderson KC, Munshi NC. Immmunomodulatory drug costimulates T cells via the B7-CD28 pathway. Blood 2004;103:1787-90.
- Tassone P, Gozzini A, Goldmacher V, Shammas MA, Whiteman KR, Carrasco DR, Li C, Allam CK, Venuta S, Anderson KC, Munshi NC. In vitro and in vivo activity of the maytansinoid immunoconjugate huN901-DM1 against CD56+ multiple myeloma cells. Cancer Res 2004;64:4629-36.
- Tassone P, Neri P, Kutok J, Burger R, Carrasco R, Goldmacher VS, Fram R, Catley L, Jacob GS, Venuta S, Anderson KC, Munshi NC. A clinically relevant SCID-hu in vivo model of human multiple myeloma. Blood 2005;106:713-6.
- Shammas MA, Reis RJS, Li C, Koley H, Hurley LC, Anderson KC, Munshi NC. Telomerase inhibition and cell growth arrest following telomestatin treatment in multiple myeloma. Clin Cancer Res 2004;10:770-6.
- Munshi NC, Hideshima T, Carrasco R, Shammas M, Auclair D, Davies F, Mitsiades N, Mitsiades C, Kim RS, Li C, Rajkumar SV, Fonseca R, Bergsagel L, Chauhan D, Anderson KC. Identification of genes modulated in multiple myeloma using genetically identical twin samples. Blood 2004;103:1799-806.
- Prabhala RH, Neri P, Bae JE, Tassone P, Shammas MA, Allam CK, Daley JF, Chauhan D, Blanchard E, Thatte HS, Anderson K, Munshi NC. Dysfunctional T regulatory cells in multiple myeloma. Blood 2005; Epub ahead of print.
- Neelapu SS, Munshi NC, Jagannath S, Watson TM, Pennington R, Reynolds C, Barlogie B, Kwak LW. Tumor antigen immunization of sibling stem cell transplant donors in multiple myeloma. Bone Marrow Transplant 2005;36:315-23.
- Tassone, Pierfrancesco, MD
- Song, Weihua, MD
- Blotta, Simona, MD
- Mancini, Valentina, MD
- Bae, Jooeun, Ph.D.
- Neri, Ernesta Paola, MD