DF/HCC Program Affiliation

Member, Leukemia Program
Member, Cancer Immunology Program

DF/HCC Associations

Associate Director, Core Facilities, EC
Member, Center Scientific Council
Director, Cell Manipulation Core

Research Abstract

Hematopoietic stem cell transplantation provides effective therapy for patients with a variety of hematologic malignancies, but this continues to be a very intensive and potentially dangerous treatment approach. With recent improvements in supportive care, the most common causes of treatment failure are disease relapse and infectious complications associated with immune deficiency following transplant. To address these 2 issues, my laboratory research is focused on the characterization of immune reconstitution following allogeneic hematopoietic stem cell transplantation. It is now well established that reconstitution of donor hematopoiesis not only replaces the recipients own immune system but also results in the development of immunity against patient tumor cells. This development of anti-tumor immunity is very effective and plays an important role in the prevention of relapse following stem cell transplantation. Both laboratory projects and clinical trials are attempting to define the immunologic mechanisms as well as the target antigens of this response. With better understanding of the mechanisms and target specificity of the graft-versus-leukemia (GVL) response, it will be possible to distinguish GVL from graft-versus-host disease (GVHD) and to develop new methods for selectively enhancing GVL.

Publications

• Sarantopoulos S, Stevenson KE, Kim HT, Bhuiya NS, Cutler CS, Soiffer RJ, Antin JH, Ritz J. High levels of B-cell activating factor in patients with active chronic graft-versus-host disease. Clin Cancer Res 2007 Oct 15; 13(20):6107-14
  PMID: 17947475
• Mullally A, Ritz J. Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation. Blood 2007 Feb 15; 109(4):1355-62
  PMID: 17008540
• Wu CJ, Ritz J. Induction of tumor immunity following allogeneic stem cell transplantation. Adv Immunol 2006; 90:133-73
  PMID: 16730263
• Zorn E, Nelson EA, Mohseni M, Porcheray F, Kim H, Litsa D, Bellucci R, Raderschall E, Canning C, Soiffer RJ, Frank DA, Ritz J. IL-2 regulates FOXP3 expression in human CD4+CD25+ regulatory T cells through a STAT dependent mechanism and induces the expansion of these cells in vivo. Blood 2006 Apr 27;
  PMID: 16645171
• Zorn E, Kim HT, Lee SJ, Floyd BH, Litsa D, Arumugarajah S, Bellucci R, Alyea EP, Antin JH, Soiffer RJ, Ritz J. Reduced frequency of FOXP3+ CD4+CD25+ regulatory T cells in patients with chronic graft-versus-host disease. Blood 2005 Oct 15; 106(8):2903-11
  PMID: 15972448
• Wu CJ, Biernacki M, Kutok JL, Rogers S, Chen L, Yang XF, Soiffer RJ, Ritz J. Graft-versus-leukemia target antigens in chronic myelogenous leukemia are expressed on myeloid progenitor cells. Clin Cancer Res 2005 Jun 15; 11(12):4504-11
  PMID: 15958636
• Bellucci R, Alyea EP, Chiaretti S, Wu CJ, Zorn E, Weller E, Wu B, Canning C, Schlossman R, Munshi NC, Anderson KC, Ritz J. Graft-versus-tumor response in patients with multiple myeloma is associated with antibody response to BCMA, a plasma-cell membrane receptor. Blood 2005 May 15; 105(10):3945-50
  PMID: 15692072
• Miklos DB, Kim HT, Miller KH, Guo L, Zorn E, Lee SJ, Hochberg EP, Wu CJ, Alyea EP, Cutler C, Ho V, Soiffer RJ, Antin JH, Ritz J. Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission. Blood 2005 Apr 1; 105(7):2973-8
  PMID: 15613541
• Zorn E, Miklos DB, Floyd BH, Mattes-Ritz A, Guo L, Soiffer RJ, Antin JH, Ritz J. Minor Histocompatibility Antigen DBY Elicits a Coordinated B and T Cell Response after Allogeneic Stem Cell Transplantation. J Exp Med 2004 Apr 19; 199(8):1133-42
  PMID: 15096539
• Bellucci R, Wu CJ, Chiaretti S, Weller E, Davies FE, Alyea EP, Dranoff G, Anderson KC, Munshi NC, Ritz J. Complete response to donor lymphocyte infusion in multiple myeloma is associated with antibody responses to highly expressed antigens. Blood 2004 Jan 15; 103(2):656-63
  PMID: 14563636
• Miklos DB, Kim HT, Zorn E, Hochberg EP, Guo L, Mattes-Ritz A, Viatte S, Soiffer RJ, Antin JH, Ritz J. Antibody response to DBY minor histocompatibility antigen is induced after allogeneic stem cell transplantation and in healthy female donors. Blood 2004 Jan 1; 103(1):353-9
  PMID: 14512314
• Orsini E, Bellucci R, Alyea EP, Schlossman R, Canning C, McLaughlin S, Ghia P, Anderson KC, Ritz J. Expansion of tumor-specific CD8+ T cell clones in patients with relapsed myeloma after donor lymphocyte infusion. Cancer Res 2003 May 15; 63(10):2561-8
  PMID: 12750280
• Hochberg EP, Miklos DB, Neuberg D, Eichner DA, McLaughlin SF, Mattes-Ritz A, Alyea EP, Antin JH, Soiffer RJ, Ritz J. A novel rapid single nucleotide polymorphism (SNP)-based method for assessment of hematopoietic chimerism after allogeneic stem cell transplantation. Blood 2003 Jan 1; 101(1):363-9
  PMID: 12393452
• Bellucci R, Alyea EP, Weller E, Chillemi A, Hochberg E, Wu CJ, Canning C, Schlossman R, Soiffer RJ, Anderson KC, Ritz J. Immunologic effects of prophylactic donor lymphocyte infusion after allogeneic marrow transplantation for multiple myeloma. Blood 2002 Jun 15; 99(12):4610-7
  PMID: 12036895
• Hochberg EP, Chillemi AC, Wu CJ, Neuberg D, Canning C, Hartman K, Alyea EP, Soiffer RJ, Kalams SA, Ritz J. Quantitation of T-cell neogenesis in vivo after allogeneic bone marrow transplantation in adults. Blood 2001 Aug 15; 98(4):1116-21
  PMID: 11493459
• Wu CJ, Yang XF, McLaughlin S, Neuberg D, Canning C, Stein B, Alyea EP, Soiffer RJ, Dranoff G, Ritz J. Detection of a potent humoral response associated with immune-induced remission of chronic myelogenous leukemia. J Clin Invest 2000 Sep; 106(5):705-14
  PMID: 10974024