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Ivan Marques Borrello, M.D.
Associate Professor of Oncology
Languages: English, Italian, Portuguese, Spanish
Expertise: Bone Marrow Transplant, Clinical Trials, Hematologic Malignancies, Immunotherapy, Medical Oncology, Multiple Myeloma
Research Interests: Immunotherapy in Multiple Myeloma and Acute Myeloid Leukemia
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Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Appointment Phone: 410-955-8964
401 N. Broadway
Baltimore, MD 21231 map
Dr. Borrello's group has evidence of the development of an autologous graft vs. tumor effect early post-transplant that can be maintained by tumor-specific vaccinations. Explanations for these observations include evidence that T cell immune responsiveness is restored with transplantation through the reversal of T cell tolerance mediated through a variety of factors present in the transplanted host. A major focus of his work now is based on identifying the mechanisms mediating this enhanced antitumor activity, further enhancing immune-based therapies through in vitro and in vivo immune interventions, and developing a non-myeloablative platform in which these therapies can be delivered with similar efficacy but less toxicity. This work has direct applicability to the development of future clinical studies. Specifically, this work has established the importance of utilizing a lymphopenic host in the development of adoptive immunotherapeutic strategies. This preclinical model, coupled to the development of a universal bystander GM-CSF secreting vaccine developed by Dr, Borrello, has now been used in two currently ongoing clinical studies: one in patients with multiple myeloma and the second in patients with acute myeloid leukemia.
A major hurdle in tumor immunotherapy is how to deliver a cellular product with stringent tumor specificity. Evidence of the enhanced tumor specificity of activated marrow infiltrating lymphocytes (MILs) as compared with activated peripheral blood lymphocytes suggests a strategy of easily developing antigen-specific T cell adoptive immunotherapeutic strategies with minimal interventions and may well represent a significant advance in the development of a polyvalent, highly enriched tumor-specific population. The advantage of such an approach is to deliver immunotherapy marked by enhanced tumor-specificity and T cell responsiveness. His group has demonstrated that the T cells from the tumor/bone marrow microenvironment display evidence of marked tumor-specificity, yet are lacking endogenous tumor-specific reactivity. In contrast, the in vitro activation of these cells with beads containing anti-CD3/anti-CD28 is capable of activating these cells and expanding them while still maintaining marked antitumor specificity. This strategy is an approach that will hopefully represent a significant advance in the development of tumor-specific adoptive immunotherapeutic interventions starting with the treatment of multiple myeloma but with broad applicability to numerous other hematologic diseases.
Tumor vaccines have typically been utilized as an approach to enhance antigen specificity of T cells in an effort to impart a potent antitumor effect. GM-CSF-based vaccines have been utilized in several clinical trials. Until recently, an extensive body of literature existed to suggest the minimal amount of GM-CSF required to generate effective antitumor responses. Murine data is now emerging identifying a maximal threshold as well above which these vaccines induce myeloid suppressor cells capable of inhibiting a T cell response. This is the first such evidence to demonstrate a therapeutic ceiling for vaccines that will be important in designing subsequent clinical studies. Pharmacologic agents capable of inhibiting the function of the myeloid suppressor cells are also actively being investigated.
In his latest studies, Dr. Borrello has added a multiple myeloma-specific version of the Johns Hopkins-developed vaccine, called GVAX, to further engage the immune system to attack cancer cells. This vaccine is a version of those already successfully used at the Johns Hopkins Kimmel Cancer Center to treat pancreas, prostate, and breast cancers.
The vaccine acts as the commander that instructs the immune system to fight the cancer. But without a strong force of cancer-specific T-cells to carry out the immune attack, the vaccine cant get the job done. So, were finding MILS are helpful here, too. The vaccine stimulates the immune system to order an attack, and the MILs respond to the command and specifically seek out and destroy cancer cells.
- Associate Professor of Oncology
Departments / Divisions
- Oncology - Immunology and Hematopoiesis
Centers & Institutes
- MD, Medical College of Virginia School of Medicine (1992)
- University of Chicago Pritzker School of Medicine / Internal Medicine (1995)
- Johns Hopkins University School of Medicine / Oncology (1998)
Research & Publications
Clinical Trial Keywordsmultiple myeloma
Selected PublicationsJournal Citations
Huff, C.A.; Fuchs, E.J.; Smith, B.D.; Blackford, A.; Garrett-Mayer, E.; Brodsky, R.A.; Flinn, I.W.; Ambinder, R.F.; Borrello, I.M.; Matsui, W.H.; Vogelsang, G.B.; Griffin, C.A.; Luznik, L.; Jones, R.J. Graft-versus-host reactions and the effectiveness of donor lymphocyte infusions. Biol Blood Marrow Transplant. 2006 Apr;12(4):414-421.
Serafini, P.; Borrello, I.; Bronte, V. Myeloid suppressor cells in cancer: recruitment, phenotype, properties, and mechanisms of immune suppression. Semin Cancer Biol. 2006 Feb;16(1):53-65.
Serafini, P.; Meckel, K.; Kelso, M.; Noonan, K.; Califano, J.; Koch, W.; Dolcetti, L.; Bronte, V.; Borrello, I. Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J Exp Med. 2006 Nov 27;203(12):2691-2702.
Bolanos-Meade, J.; Garrett-Mayer, E.; Luznik, L.; Anders, V.; Webb, J.; Fuchs, E.J.; Huff, C.A.; Matsui, W.; Borrello, I.M.; Brodsky, R.; Kasamon, Y.L.; Swinnen, L.J.; Flinn, I.W.; Ambinder, R.F.; Jones, R.J.; Hess, A.D.; Vogelsang, G.B. Induction of autologous graft-versus-host disease: results of a randomized prospective clinical trial in patients with poor risk lymphoma. Biol Blood Marrow Transplant. 2007 Oct;13(10):1185-1191.
Chaudhry, V.; Cornblath, D.R.; Polydefkis, M.; Ferguson, A.; Borrello, I. Characteristics of Bortezomib- and Thalidomide-induced peripheral neuropathy. . J Peripher Nerv Syst. 2008 Dec 2008;13:275-282.
Luznik, L.; O'Donnell, P.V.; Symons, H.J.; Chen, A.R.; Leffell, M.S.; Zahurak, M.; Gooley, T.A.; Piantadosi, S.; Kaup, M.; Ambinder, R.F.; Huff, C.A.; Matsui, W.; Bolanos-Meade, J.; Borrello, I.; Powell, J.D.; Harrington, E.; Warnock, S.; Flowers, M.; Brodsky, R.A.; Sandmaier, B.M.; Storb, R.F.; Jones, R.J.; Fuchs, E.J. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008 Jun;14(6):641-650.
Matsui, W.; Wang, Q.; Barber, J.P.; Brennan, S.; Smith, B.D.; Borrello, I.; McNiece, I.; Lin, L.; Ambinder, R.F.; Peacock, C.; Watkins, D.N.; Huff, C.A.; Jones, R.J. Clonogenic multiple myeloma progenitors, stem cell properties, and drug resistance. Cancer Res. 2008 Jan 1;68(1):190-197.
Mirmonsef, P.; Tan, G.; Zhou, G.; Morino, T.; Noonan, K.; Borrello, I.; Levitsky, H.I. Escape from suppression: tumor-specific effector cells outcompete regulatory T cells following stem-cell transplantation. Blood. 2008 Feb 15;111(4):2112-2121.
Serafini, P.; Mgebroff, S.; Noonan, K.; Borrello, I. Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells. Cancer Res. 2008 Jul 1;68(13):5439-5449.
Warlick, E.D.; O'Donnell, P.V.; Borowitz, M.; Grupka, N.; Decloe, L.; Garrett-Mayer, E.; Borrello, I.; Brodsky, R.; Fuchs, E.; Huff, C.A.; Luznik, L.; Matsui, W.; Ambinder, R.; Jones, R.J.; Douglas Smith, B. Myeloablative allogeneic bone marrow transplant using T cell depleted allografts followed by post-transplant GM-CSF in high-risk myelodysplastic syndromes. Leuk Res. 2008 Sep;32(9):1439-1447.
Borrello, I. Lenalidomide in renal insufficiency - balancing the risks and benefits. Br J Haematol. 2009 Feb 1;144(3):446-447.
Borrello, I.M.; Levitsky, H.I.; Stock, W.; Sher, D.; Qin, L.; DeAngelo, D.J.; Alyea, E.P.; Stone, R.M.; Damon, L.E.; Linker, C.A.; Maslyar, D.J.; Hege, K.M. Granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML). Blood. 2009 Aug 27;114(9):1736-1745.
Kasamon, Y.L.; Luznik, L.; Leffell, M.S.; Kowalski, J.; Tsai, H.L.; Bolanos-Meade, J.; Morris, L.E.; Crilley, P.A.; O'Donnell, P.V.; Rossiter, N.; Huff, C.A.; Brodsky, R.A.; Matsui, W.H.; Swinnen, L.J.; Borrello, I.; Powell, J.D.; Ambinder, R.F.; Jones, R.J.; Fuchs, E.J. Nonmyeloablative HLA-Haploidentical BMT with High-Dose Posttransplantation Cyclophosphamide: Effect of HLA Disparity on Outcome. Biol Blood Marrow Transplant. 2009 Nov 16.
Chanan-Khan, A.A.; Borrello, I.; Lee, K.P.; Reece, D.E. Development of target-specific treatments in multiple myeloma. Br J Haematol. 2010 Oct;151(1):3-15.
Fonseca, R.; Richardson, P.; Giralt, S.; Lonial, S.; Rajkumar, S.V.; Stewart, A.K.; Bensinger, W.; Somlo, G.; Vescio, R.; Mikhael, J.; Reeder, C.; Tiedemann, R.; Tricot, G.; Rifkin, R.; Shaughnessy, J.; Munshi, N.; Raje, N.; Ghobrial, I.; Laubach, J.; Schlossman, R.; Treon, S.; Mahindra, A.; Avigan, D.; Rosenblatt, J.; Jagannath, S.; Niesvizky, R.; Landau, H.; Chen-Kiang, S.; Siegel, D.S.; Zimmerman, T.; Mehta, J.; Vesole, D.; Rosen, S.; Hofmeister, C.; Lacy, M.; Dispenzieri, A.; Borrello, I.; Hayman, S.R.; Kumar, S.; Buadi, F.; Dingli, D.; Russell, S.; Melissa Alsina, M.A.; Fernandez, H.; Roy, V.; Pereira, D.; Stadtmauer, E.; Vij, R.; Jakubowiak, A.; Lentzsch, S.; Song, K.; Trudel, S.; Chen, C.; Reece, D.; Stewart, D.; Singhal, S.; Comenzo, R.; Gertz, M.A.; Greipp, P.R.; Durie, B.; Barlogie, B.; Anderson, K.; Dalton, W.; Coleman, M.; Novis, S.; Kyle, R.A. Conflicts of interest, authorship, and disclosures in industry-related scientific publications. Mayo Clin Proc. 2010 Feb;85(2):197-199; author reply 201-194.
Kasamon, Y.L.; Luznik, L.; Leffell, M.S.; Kowalski, J.; Tsai, H.L.; Bolanos-Meade, J.; Morris, L.E.; Crilley, P.A.; O'Donnell, P.V.; Rossiter, N.; Huff, C.A.; Brodsky, R.A.; Matsui, W.H.; Swinnen, L.J.; Borrello, I.; Powell, J.D.; Ambinder, R.F.; Jones, R.J.; Fuchs, E.J. Nonmyeloablative HLA-haploidentical bone marrow transplantation with high-dose posttransplantation cyclophosphamide: effect of HLA disparity on outcome. Biol Blood Marrow Transplant. 2010 Apr;16(4):482-489.
Luznik, L.; Bolanos-Meade, J.; Zahurak, M.; Chen, A.R.; Smith, B.D.; Brodsky, R.; Huff, C.A.; Borrello, I.; Matsui, W.; Powell, J.D.; Kasamon, Y.; Goodman, S.N.; Hess, A.; Levitsky, H.I.; Ambinder, R.F.; Jones, R.J.; Fuchs, E.J. High-dose cyclophosphamide as single-agent, short-course prophylaxis of graft-versus-host disease. Blood. 2010 Apr 22;115(16):3224-3230.
Noonan, K.; Marchionni, L.; Anderson, J.; Pardoll, D.; Roodman, G.D.; Borrello, I. A novel role of IL-17-producing lymphocytes in mediating lytic bone disease in multiple myeloma. Blood. 2010 Nov 4;116(18):3554-3563.