Christene A. Huang, PhD

Massachusetts General Hospital

Massachusetts General Hospital
Phone: (617) 726-6505
Fax: (617) 726-4067


cahuang@mgh.harvard.edu

Christene A. Huang, PhD

Massachusetts General Hospital

EDUCATIONAL TITLES

  • Associate Professor, Surgery, Harvard Medical School
  • Associate Immunologist, Surgery, Massachusetts General Hospital
  • Scientific Co-Director, Recombinant Protein Expression and Purification Core Facility, Dana-Farber/Harvard Cancer Center

DF/HCC PROGRAM AFFILIATION

Research Abstract

Hematopoietic cell transplantation (HCT) can be an effective approach to induce allograft tolerance, replace defective blood lineages and cure hematological malignancies. Unfortunately, the toxicities associated with HCT protocols that reliably establish stable engraftment limit this approach in the clinic. Toxicities include complications resulting from cytotoxic conditioning and graft versus host disease (GvHD). One of my major scientific achievements has been the development of a novel, minimally toxic protocol that reliably establishes hematopoietic stem cell engraftment and tolerance across haploidentical MHC barriers in miniature swine without GvHD. As a confirmation of the clinical relevance of the miniature swine model, haploidentical HCT following standard myeloablation uniformly results in severe GvHD and/or hematopoietic failure. Preliminary data from my research suggest that mild HCT protocols that preserve regulatory T-cell development and function may be more successful in achieving stable donor stem cell engraftment while avoiding GvHD than those that rely on harsh conditioning and complete donor and host T-cell depletion. Another major scientific achievement has been the establishment of several leukemia and lymphoma cell lines derived from the bone marrow of older miniature swine that spontaneously developed chronic myelogenous leukemia over the past ten years as well as from experimental animals that developed post-transplantation lymphoproliferative disorder. Recently one of the myeloid leukemia cell lines demonstrated growth in vivo when injected intraosseously into MHC-matched miniature swine. The goal of these tumor studies is to develop transplantable tumor models in miniature swine to enable direct assessment of tumor immunotherapy in a clinically relevant large animal model.

Publications

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  • Wang Z, Wei M, Zhang H, Chen H, Germana S, Huang CA, Madsen JC, Sachs DH, Wang Z. Diphtheria-toxin based anti-human CCR4 immunotoxin for targeting human CCR4(+) cells in vivo. Mol Oncol 2015. PubMed
  • Madariaga ML, Michel SG, La Muraglia GM, Sihag S, Leonard DA, Farkash EA, Colvin RB, Cetrulo CL, Huang CA, Sachs DH, Madsen JC, Allan JS. Recipient-Matching of Passenger Leukocytes Prolongs Survival of Donor Lung Allografts in Miniature Swine. Transplantation 2015. PubMed
  • Mathes DW, Solari MG, Gazelle GS, Butler PE, Wu A, Nazzal A, Nielsen GP, Huang CA, Sachs DH, Lee WP, Randolph MA. Stable mixed hematopoietic chimerism permits tolerance of vascularized composite allografts across a full major histocompatibility mismatch in swine. Transpl Int 2014; 27:1086-96. PubMed
  • Wei M, Marino J, Trowell A, Zhang H, Stromp Peraino J, Rajasekera PV, Madsen JC, Sachs DH, Huang CA, Benichou G, Wang Z. Diphtheria toxin-based recombinant murine IL-2 fusion toxin for depleting murine regulatory T cells in vivo. Protein Eng. Des. Sel. 2014; 27:289-95. PubMed
  • Peraino JS, Zhang H, Rajasekera PV, Wei M, Madsen JC, Sachs DH, Huang CA, Wang Z. Diphtheria toxin-based bivalent human IL-2 fusion toxin with improved efficacy for targeting human CD25(+) cells. J Immunol Methods 2014; 405:57-66. PubMed
  • Peraino JS, Schenk M, Li G, Zhang H, Farkash EA, Sachs DH, Huang CA, Duran-Struuck R, Wang Z. Development of a diphtheria toxin-based recombinant porcine IL-2 fusion toxin for depleting porcine CD25+ cells. J Immunol Methods 2013; 398-399:33-43. PubMed
  • Wamala I, Matar AJ, Farkash E, Wang Z, Huang CA, Sachs DH. Recombinant anti-monkey CD3 immunotoxin depletes peripheral lymph node T lymphocytes more effectively than rabbit anti-thymocyte globulin in na誰ve baboons. Transpl Immunol 2013; 29:60-3. PubMed
  • Peraino JS, Schenk M, Zhang H, Li G, Hermanrud CE, Neville DM, Sachs DH, Huang CA, Duran-Struuck R, Wang Z. A truncated diphtheria toxin based recombinant porcine CTLA-4 fusion toxin. J Immunol Methods 2013. PubMed
  • Pathiraja V, Matar AJ, Gusha A, Huang CA, Duran-Struuck R. Leukapheresis protocol for nonhuman primates weighing less than 10 kg. J Am Assoc Lab Anim Sci 2013; 52:70-7. PubMed
  • Duran-Struuck R, Matar A, Crepeau R, Gusha A, Schenk M, Hanekamp I, Pathiraja V, Spitzer TR, Sachs DH, Huang CA. Lack of antidonor alloantibody does not indicate lack of immune sensitization: studies of graft loss in a haploidentical hematopoietic cell transplantation Swine model. Biol Blood Marrow Transplant 2012; 18:1629-37. PubMed
  • Crepeau R, Matar A, Spitzer TR, Robson S, Pathiraja V, Sachs DH, Huang CA, Duran-Struuck R. Edema and tetraparesis in a miniature pig after allogeneic hematopoietic cell transplantation. Comp Med 2012; 62:298-302. PubMed
  • Matar AJ, Pathiraja V, Wang Z, Duran-Struuck R, Gusha A, Crepeau R, Tasaki M, Sachs DH, Huang CA. Effect of pre-existing anti-diphtheria toxin antibodies on T cell depletion levels following diphtheria toxin-based recombinant anti-monkey CD3 immunotoxin treatment. Transpl Immunol 2012; 27:52-4. PubMed
  • Matar AJ, Crepeau RL, Pathiraja V, Robson S, Fishman JA, Spitzer TR, Sachs DH, Huang CA, Duran-Struuck R. Effects of mobilization regimens in donors on outcomes of hematopoietic cell transplantation in miniature Swine. Comp Med 2013; 62:487-94. PubMed
  • Hermanrud CE, Lucas CL, Sykes M, Huang CA, Wang Z. Expression and purification of soluble murine CD40L monomers and polymers in yeast Pichia pastoris. Protein Expr Purif 2010; 76:115-20. PubMed
  • Lutton BV, Cho PS, Hirsh EL, Ferguson KK, Teague AG, Hanekamp JS, Chi N, Goldman SN, Messina DJ, Houser S, Yeap BY, Popma SH, Sachs DH, Huang CA. Approaches to avoid immune responses induced by repeated subcutaneous injections of allogeneic umbilical cord tissue-derived cells. Transplantation 2011; 90:494-501. PubMed
  • Duran-Struuck R, Cho PS, Teague AG, Fishman B, Fishman AS, Hanekamp JS, Moran SG, Wikiel KJ, Ferguson KK, Lo DP, Duggan M, Arn JS, Billiter B, Horner B, Houser S, Yeap BY, Westmoreland SV, Spitzer TR, McMorrow IM, Sachs DH, Bronson RT, Huang CA. Myelogenous leukemia in adult inbred MHC-defined miniature swine: A model for human myeloid leukemias. 2010; 135:243-56. PubMed
  • Cho PS, Messina DJ, Hirsh EL, Chi N, Goldman SN, Lo DP, Harris IR, Popma SH, Sachs DH, Huang CA. Immunogenicity of umbilical cord tissue derived cells. Blood 2007; 111:430-8. PubMed
  • Cho PS, Lo DP, Wikiel KJ, Rowland HC, Coburn RC, McMorrow IM, Goodrich JG, Arn JS, Billiter RA, Houser SL, Shimizu A, Yang YG, Sachs DH, Huang CA. Establishment of transplantable porcine tumor cell lines derived from MHC-inbred miniature swine. Blood 2007; 110:3996-4004. PubMed
  • Horner BM, Cina RA, Wikiel KJ, Lima B, Ghazi A, Lo DP, Yamada K, Sachs DH, Huang CA. Predictors of organ allograft tolerance following hematopoietic cell transplantation. Am J Transplant 2007; 6:2894-902. PubMed
  • Cina RA, Wikiel KJ, Lee PW, Cameron AM, Hettiarachy S, Rowland H, Goodrich J, Colby C, Spitzer TR, Neville DM, Huang CA. Stable multilineage chimerism without graft versus host disease following nonmyeloablative haploidentical hematopoietic cell transplantation. Transplantation 2006; 81:1677-85. PubMed
  • Cho PS, Mueller NJ, Cameron AM, Cina RA, Coburn RC, Hettiaratchy S, Melendy E, Neville DM, Patience C, Fishman JA, Sachs DH, Huang CA. Risk factors for the development of post-transplant lymphoproliferative disorder in a large animal model. Am J Transplant 2004; 4:1274-82. PubMed
  • Lima B, Gleit ZL, Cameron AM, Germana S, Murphy MC, Consorti R, Chang Q, Down JD, LeGuern C, Sachs DH, Huang CA. Engraftment of quiescent progenitors and conversion to full chimerism after nonmyelosuppressive conditioning and hematopoietic cell transplantation in miniature swine. Biol Blood Marrow Transplant 2003; 9:571-82. PubMed
  • Goltz M, Ericsson T, Patience C, Huang CA, Noack S, Sachs DH, Ehlers B. Sequence analysis of the genome of porcine lymphotropic herpesvirus 1 and gene expression during posttransplant lymphoproliferative disease of pigs. Virology 2002; 294:383-93. PubMed
  • Huang CA, Fuchimoto Y, Gleit ZL, Ericsson T, Griesemer A, Scheier-Dolberg R, Melendy E, Kitamura H, Fishman JA, Ferry JA, Harris NL, Patience C, Sachs DH. Posttransplantation lymphoproliferative disease in miniature swine after allogeneic hematopoietic cell transplantation: similarity to human PTLD and association with a porcine gammaherpesvirus. Blood 2001; 97:1467-73. PubMed
  • Fuchimoto Y, Huang CA, Yamada K, Shimizu A, Kitamura H, Colvin RB, Ferrara V, Murphy MC, Sykes M, White-Scharf M, Neville DM, Sachs DH. Mixed chimerism and tolerance without whole body irradiation in a large animal model. J Clin Invest 2000; 105:1779-89. PubMed
  • Huang CA, Fuchimoto Y, Scheier-Dolberg R, Murphy MC, Neville DM, Sachs DH. Stable mixed chimerism and tolerance using a nonmyeloablative preparative regimen in a large-animal model. J Clin Invest 2000; 105:173-81. PubMed
  • Peraino JS, Hermanrud CE, Springett L, Zhang H, Li G, Srinivasan S, Gusha A, Sachs DH, Huang CA, Wang Z. Expression and characterization of recombinant soluble porcine CD3 ectodomain molecules: mapping the epitope of an anti-porcine CD3 monoclonal antibody 898H2-6-15. Cell Immunol 2012; 276:162-7. PubMed
  • Liang F, Wamala I, Scalea J, Tena A, Cormack T, Pratts S, Duran-Struuck R, Elias N, Hertl M, Huang CA, Sachs DH. Increased levels of anti-non-Gal IgG following pig-to-baboon bone marrow transplantation correlate with failure of engraftment. Xenotransplantation 2013; 20:458-68. PubMed
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