Ivan Borrello, M.D.
Assistant Professor in Oncology
Bunting-Blaustein Cancer Research Building , Room 453
Tel: (410) 955- 4967
Fax: (443) 287-4653
Email: borreiv@jhmi.edu

Research Focus :

Our group is focused on understanding the immune response occurring within the bone marrow and developing strategies to utilize the marrow infiltrating lymphocytes (MILs) for adoptive immunotherapy. A variety of clinical studies have been carried out to date utilizing peripheral blood T cells (PBLs) activated and expanded with anti-CD3/CD28 bound to magnetic beads. Although this approach has been able to effectively expand T cell numbers, a major limitation is the lack of antigen specificity. Our initial observations in myeloma patients demonstrated significantly greater tumor specificity of MILs compared to PBLs following anti-CD3/CD28 activation. Furthermore, these T cells possess surface expression markers that facilitated their trafficking to the marrow and they also appear to target and kill myeloma stem cell precursors in addition to mature plasma cells. Our laboratory research is currently attempting to determine which component of the bone marrow microenvironment is responsible for the augmented T cell response. Utilizing samples from myeloma patients, we are examining the individual components of both T cells and bone marrow stromal factors involved in this response. This will be done utilizing both genetic expression profiling as well as a proteomic analysis. In attempting to understand the mechanisms mediating heightened immune responsiveness, we are also examining the role of bone marrow in mediating tumor-induced T cell tolerance utilizing a transgenic antigen-specific murine model. We are also planning to use these observations in planning subsequent clinical trials especially in multiple myeloma.

Selected Publications :

• Borrello I, Sotomayor E, Cooke S, Tubb E, Levitsky H. A universal granulocye-macrophage colony-stimulating factor-producing bystander cell line for use in the formulation of autologous tumor cell-base vaccines. Human Gene Therapy 1999 Aug;10(12):983-1991.
• Borrello I, Sotomayor E, Rattis FM, Cooke S, Gu L., Levitsky H. Sustaining the Graft-Versus-Tumor Effect Through Posttransplant Immunization with Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Producing Tumor Vaccines. Blood. 2000 May 15;95(10):3011-9.
• Serafini P, Carbley R, Noonan KA, Tan G, Bronte V,Borrello I. High-dose granulocyte macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res . 2004;64:6337-43.
• Caligiuri MA, Velardi A, Scheinberg DA, Borrello IM. Immunotherapeutic approaches for hematologic malignancies. Hematology (Am Soc Hematol Educ Program). 2004;337-53.
• Noonan K, Matsui W, Serafini P, Carbley R, Tan G, Khalili J, Bonyhadi M, Levitsky H, Whartenby K., Borrello I. Anti-myeloma Activity of Activated Marrow Infiltrating Lymphocytes: A Novel Approach to Adoptive Immunotherapy. Canc Res 2005;65:2026-34.