Massachusetts General Hospital

Harry E. Rubash, MD

Harry E. Rubash, M.D.

Edith M. Ashley Professor of Orthopaedic Surgery
Harvard Medical School

2011-12 Chief's Report

Monoclonal Antibody & Immunotherapy Laboratory

The Monoclonal Antibody & Immunotherapy Laboratory is under the co-direction of Drs. Soldano Ferrone, Cristina Ferrone, Joseph H. Schwab, and Xinhui Wang. The focus of the Laboratory is to investigate immunological events in the development of cancers, with a particular emphasis on musculoskeletal neoplasms such as chordoma, chondrosarcoma and osteosarcoma, and to develop targeted immunotherapy to expand and improve treatment options for patients with these tumors.


The foundation of the Monoclonal Antibody & Immunotherapy Laboratory is its variety of motivated and skilled international researchers led by Dr. Soldano Ferrone. Members of the Laboratory have extensive experience in antibody production, tumor immunology and cutting-edge techniques, including the use of a novel chimeric antigen receptor as a tool to generate cognate T-cells against tumor-specific antigens. The Laboratory is focused on clinically relevant translational research, which is aided by the clinical practices of Drs. Schwab and Ferrone, who treat patients burdened with the types of tumors studied in the Laboratory.


Dr. Ferrone leads the Laboratory, bringing extensive experience of 40 years of funded research. He has been chairman both at New York Medical College’s Department of Microbiology and Immunology as well as at Roswell Park Cancer Center’s Department of Immunology. He has over 900 peer-reviewed publications and has written scores of books on the subject of cancer immunology. It is his belief that research will be clinically relevant only if it involves clinician scientists who are closest to patients.


An exciting recent development in the Laboratory stems from an unexpected observation made by Dr. Schwab along with Dr. Petur Nielsen, Chief of Musculoskeletal Pathology at MGH. These two investigators found that a majority of resected chordoma specimens possess tumor-infiltrating lymphocytes. This new discovery in chordoma suggests that patients may develop an immune response to their own tumor. Additionally, taking advantage of a unique collection of monoclonal antibodies available in the Laboratory, they have found that a subset of chordoma tumor specimens possess human leukocyte antigen (HLA) class I antigen processing machinery defects, suggesting a possible escape mechanism from immune recognition exhibited by chordoma.


Another research area that is being actively developed takes advantage of the collection of tumor antigen-specific monoclonal antibodies Dr. Ferrone’s Laboratory has developed over the years. These monoclonal antibodies are being utilized to design combinatorial immunotherapeutic strategies for the treatment of malignant diseases of orthopaedic interest. The working hypothesis being tested is that to be effective a therapy has to eradicate not only differentiated cancer cells, but also cancer initiating cells. According to the cancer stem cell theory, these cells, which are resistant to chemo- and radiotherapy and are highly tumorigenic in immunodeficient mice, play a major role in disease recurrence and metastatic spread.


The extensive expertise that is available within the Laboratory is not only used to conduct high-quality research but also to train future leaders of translational research at MGH. Dr. Harry Rubash encouraged the Laboratory to explore training options for motivated Harvard Medical students, and Dr. Ferrone responded by accepting two new students into the Laboratory who work directly with Dr. Schwab. Shalin Patel, a Harvard Medical student, has joined the laboratory and is at the beginning of his medical career. He already has extensive experience in basic science and is planning to apply his expertise to a career in orthopaedic oncology. Shalin’s main interest is the quest for treatment targets for chordoma. Another member of the research team is Sjoerd Nota, a research fellow from the Netherlands. Sjoerd is a young physician working toward his PhD under the supervision of Dr. Ferrone and Dr. Schwab. Sjoerd’s aspiration to become an orthopaedic oncologist led to the establishment of a wide variety of projects addressing possible future immunotherapeutic treatment options for chondrosarcoma.


Dr. Soldano Ferrone and his team are convinced that the most effective way to achieve significant progress in the field of orthopaedic oncology is by collaborating in the collective search for future targets in the treatment of musculoskeletal neoplasms. This vision led to the formation of a widespread network of researchers and collaborations with other leading institutions all over the world.


Through these collaborations as well as sharing research findings presented at international conferences and in published papers, the Monoclonal Antibody & Immunotherapy Laboratory is proud to be able to contribute and take the lead in the progress of possible applications of immunotherapy for sarcoma.

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