Mirjam H M Heemskerk

Summary

Affiliation: Leiden University Medical Center
Country: The Netherlands

Publications

  1. pmc Generating HPV specific T helper cells for the treatment of HPV induced malignancies using TCR gene transfer
    Kirsten B J Scholten
    Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
    J Transl Med 9:147. 2011
  2. pmc Dual HLA class I and class II restricted recognition of alloreactive T lymphocytes mediated by a single T cell receptor complex
    M H Heemskerk
    Department of Hematology, Leiden University Medical Center, C2 R, P O Box 9600, 2300 RC Leiden, The Netherlands
    Proc Natl Acad Sci U S A 98:6806-11. 2001
  3. pmc Reprogramming of virus-specific T cells into leukemia-reactive T cells using T cell receptor gene transfer
    Mirjam H M Heemskerk
    Department of Hematology, Leiden University Medical Center, C2 R, P O Box 9600, 2300 RC, Netherlands
    J Exp Med 199:885-94. 2004
  4. ncbi Redirection of antileukemic reactivity of peripheral T lymphocytes using gene transfer of minor histocompatibility antigen HA-2-specific T-cell receptor complexes expressing a conserved alpha joining region
    Mirjam H M Heemskerk
    Department of Hematology, Leiden University Medical Center, C2 R, PO Box 9600, 2300 RC Leiden, The Netherlands
    Blood 102:3530-40. 2003
  5. ncbi Efficiency of T-cell receptor expression in dual-specific T cells is controlled by the intrinsic qualities of the TCR chains within the TCR-CD3 complex
    Mirjam H M Heemskerk
    Department of Hematology, Leiden University Medical Center, C2 R, PO Box 9600, 2300 RC Leiden, The Netherlands
    Blood 109:235-43. 2007
  6. ncbi Functional analysis of killer Ig-like receptor-expressing cytomegalovirus-specific CD8+ T cells
    Lars T van der Veken
    Department of Hematology, Laboratory of Experimental Hematology, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 182:92-101. 2009
  7. doi Allo-HLA-reactive T cells inducing graft-versus-host disease are single peptide specific
    Avital L Amir
    Department of Hematology, Leiden University Medical Center, The Netherlands
    Blood 118:6733-42. 2011
  8. ncbi Multiple myeloma-reactive T cells recognize an activation-induced minor histocompatibility antigen encoded by the ATP-dependent interferon-responsive (ADIR) gene
    Cornelis A M van Bergen
    Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Blood 109:4089-96. 2007
  9. pmc The human leukocyte antigen-presented ligandome of B lymphocytes
    Chopie Hassan
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Mol Cell Proteomics 12:1829-43. 2013
  10. doi PRAME-specific Allo-HLA-restricted T cells with potent antitumor reactivity useful for therapeutic T-cell receptor gene transfer
    Avital L Amir
    Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 17:5615-25. 2011

Collaborators

Detail Information

Publications43

  1. pmc Generating HPV specific T helper cells for the treatment of HPV induced malignancies using TCR gene transfer
    Kirsten B J Scholten
    Department of Pathology, VU University Medical Center, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands
    J Transl Med 9:147. 2011
    ..An alternative to generate HPV specific CD4+ and CD8+ T cells is TCR gene transfer...
  2. pmc Dual HLA class I and class II restricted recognition of alloreactive T lymphocytes mediated by a single T cell receptor complex
    M H Heemskerk
    Department of Hematology, Leiden University Medical Center, C2 R, P O Box 9600, 2300 RC Leiden, The Netherlands
    Proc Natl Acad Sci U S A 98:6806-11. 2001
    ..We propose that this finding may have major implications for immunotherapeutic interventions and insight into the development of autoimmune diseases...
  3. pmc Reprogramming of virus-specific T cells into leukemia-reactive T cells using T cell receptor gene transfer
    Mirjam H M Heemskerk
    Department of Hematology, Leiden University Medical Center, C2 R, P O Box 9600, 2300 RC, Netherlands
    J Exp Med 199:885-94. 2004
    ....
  4. ncbi Redirection of antileukemic reactivity of peripheral T lymphocytes using gene transfer of minor histocompatibility antigen HA-2-specific T-cell receptor complexes expressing a conserved alpha joining region
    Mirjam H M Heemskerk
    Department of Hematology, Leiden University Medical Center, C2 R, PO Box 9600, 2300 RC Leiden, The Netherlands
    Blood 102:3530-40. 2003
    ....
  5. ncbi Efficiency of T-cell receptor expression in dual-specific T cells is controlled by the intrinsic qualities of the TCR chains within the TCR-CD3 complex
    Mirjam H M Heemskerk
    Department of Hematology, Leiden University Medical Center, C2 R, PO Box 9600, 2300 RC Leiden, The Netherlands
    Blood 109:235-43. 2007
    ..In conclusion, introduced, endogenous, and chimeric TCRs compete for cell-surface expression in favor of the TCR-CD3 complex with best-pairing properties...
  6. ncbi Functional analysis of killer Ig-like receptor-expressing cytomegalovirus-specific CD8+ T cells
    Lars T van der Veken
    Department of Hematology, Laboratory of Experimental Hematology, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 182:92-101. 2009
    ..We observed no diminished general proliferative capacity and therefore we conclude that these T cells do not represent end-stage dysfunctional T cells...
  7. doi Allo-HLA-reactive T cells inducing graft-versus-host disease are single peptide specific
    Avital L Amir
    Department of Hematology, Leiden University Medical Center, The Netherlands
    Blood 118:6733-42. 2011
    ..Based on these results, we conclude that biologically relevant alloreactivity selected during in vivo immune response is peptide specific...
  8. ncbi Multiple myeloma-reactive T cells recognize an activation-induced minor histocompatibility antigen encoded by the ATP-dependent interferon-responsive (ADIR) gene
    Cornelis A M van Bergen
    Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Blood 109:4089-96. 2007
    ..In conclusion, the novel mHag LB-ADIR-1F may be a suitable target for cellular immunotherapy when applied under controlled circumstances...
  9. pmc The human leukocyte antigen-presented ligandome of B lymphocytes
    Chopie Hassan
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Mol Cell Proteomics 12:1829-43. 2013
    ..These HLA ligands can form the basis for reversed immunology approaches to identify T cell epitopes based not on in silico predictions but on the bona fide eluted HLA ligandome. ..
  10. doi PRAME-specific Allo-HLA-restricted T cells with potent antitumor reactivity useful for therapeutic T-cell receptor gene transfer
    Avital L Amir
    Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 17:5615-25. 2011
    ....
  11. doi Discovery of T cell epitopes implementing HLA-peptidomics into a reverse immunology approach
    Pleun Hombrink
    Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    J Immunol 190:3869-77. 2013
    ..The identification of LB-NISCH-1A demonstrated the technical feasibility of our approach. On the basis of these results, we present an approach that can be of value for the efficient identification of MiHA or other T cell epitopes...
  12. doi Identification of a coordinated CD8 and CD4 T cell response directed against mismatched HLA Class I causing severe acute graft-versus-host disease
    Avital L Amir
    Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    Biol Blood Marrow Transplant 18:210-9. 2012
    ..Our results demonstrate that the GVHD was mediated by a cooperative CD4 and CD8 response directed against the mismatched HLA-A2 and suggest that leukemic blasts possibly activated this CD8 and CD4 T cell response...
  13. ncbi Alphabeta T-cell receptor engineered gammadelta T cells mediate effective antileukemic reactivity
    Lars T van der Veken
    Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    Cancer Res 66:3331-7. 2006
    ..These data show that transfer of alphabetaTCRs to gammadelta T cells generated potent effector cells for immunotherapy of leukemia, without the expression of potentially hazardous mixed TCR dimers...
  14. doi Genetic engineering of virus-specific T cells with T-cell receptors recognizing minor histocompatibility antigens for clinical application
    Marieke Griffioen
    Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    Haematologica 93:1535-43. 2008
    ..The purpose of this study was to develop an optimal T-cell receptors-encoding multi-cistronic retroviral vector and an efficient method for generating T-cell receptors-engineered virus-specific T cells...
  15. ncbi Kinetic preservation of dual specificity of coprogrammed minor histocompatibility antigen-reactive virus-specific T cells
    Marleen M van Loenen
    Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    Cancer Res 69:2034-41. 2009
    ..These data imply persistence of TCR-transferred virus-specific T cells with both antileukemic and antivirus reactivity in vivo...
  16. doi Rapid re-expression of retrovirally introduced versus endogenous TCRs in engineered T cells after antigen-specific stimulation
    Marleen M van Loenen
    Department of Hematology, Leiden University Medical Center, The Netherlands
    J Immunother 34:165-74. 2011
    ..These results showed that TCR transduced T cells are functionally not different from nontransduced T cells and can potentially be used as an effective treatment strategy...
  17. pmc Hematopoiesis-restricted minor histocompatibility antigens HA-1- or HA-2-specific T cells can induce complete remissions of relapsed leukemia
    W A Erik Marijt
    Department of Hematology, Leiden University Medical Center, PO Box 9600, 2300 RC, Leiden, The Netherlands
    Proc Natl Acad Sci U S A 100:2742-7. 2003
    ..This finding implies that in vitro generated HA-1- and HA-2-specific cytotoxic T lymphocytes could be used as adoptive immunotherapy to treat hematological malignancies relapsing after alloSCT...
  18. doi Mixed functional characteristics correlating with TCR-ligand koff -rate of MHC-tetramer reactive T cells within the naive T-cell repertoire
    Pleun Hombrink
    Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Immunol 43:3038-50. 2013
    ....
  19. pmc Mixed T cell receptor dimers harbor potentially harmful neoreactivity
    Marleen M van Loenen
    Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Proc Natl Acad Sci U S A 107:10972-7. 2010
    ..In conclusion, TCR transfer results in the formation of neoreactive mixed TCR dimers with the potential to generate off-target effects, underlining the importance of searching for techniques to facilitate preferential pairing...
  20. pmc Retroviral transfer of human CD20 as a suicide gene for adoptive T-cell therapy
    Marieke Griffioen
    Department of Hematology, Laboratory of Experimental Hematology, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands
    Haematologica 94:1316-20. 2009
    ..The data support the broad value of CD20 as safety switch in adoptive T-cell therapy...
  21. ncbi Differential activation of the death receptor pathway in human target cells induced by cytotoxic T lymphocytes showing different kinetics of killing
    Jeltje F de Vries
    Department of Hematology, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
    Haematologica 92:1671-8. 2007
    ..Controversy exists whether, in addition to PFN/GrB-mediated apoptosis, death receptor-induced apoptosis contributes to the elimination of human tumor cells by CTL...
  22. pmc Optimization of the HA-1-specific T-cell receptor for gene therapy of hematologic malignancies
    Marleen M van Loenen
    Department of Hematology, Leiden University Medical Center C2 R, PO Box 9600 2300 RC Leiden, The Netherlands
    Haematologica 96:477-81. 2011
    ..Previously, however, we have demonstrated that gene transferred HA-1-TCRs are poorly expressed at the cell-surface. In this study several strategies were explored to improve expression of transferred HA-1-TCRs...
  23. ncbi Alpha beta T cell receptor transfer to gamma delta T cells generates functional effector cells without mixed TCR dimers in vivo
    Lars T van der Veken
    Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 182:164-70. 2009
    ..In view of increasing concerns on the potential autoimmune consequences of mixed TCR dimer formation, the testing of alphabeta TCR engineered gammadelta T cells in clinical trials seems warranted...
  24. ncbi Rapid assessment of the antigenic integrity of tetrameric HLA complexes by human monoclonal HLA antibodies
    Chantal Eijsink
    Leiden University Medical Center, Department of Immunohaematology and Bloodtransfusion, Leiden, The Netherlands
    J Immunol Methods 315:153-61. 2006
    ..A positive outcome of this mAb test ensures that tetrameric HLA class I can be used with greater confidence in subsequent functional assays...
  25. doi Allo-HLA reactivity of virus-specific memory T cells is common
    Avital L Amir
    Department of Hematology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Blood 115:3146-57. 2010
    ....
  26. doi Characterization of the T-cell-mediated immune response against the Aspergillus fumigatus proteins Crf1 and catalase 1 in healthy individuals
    Hetty Jolink
    Department of Hematology, Leiden University Medical Center, C2 P, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    J Infect Dis 208:847-56. 2013
    ....
  27. pmc Identification of varicella-zoster virus-specific CD8 T cells in patients after T-cell-depleted allogeneic stem cell transplantation
    Pim L J van der Heiden
    Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    J Virol 83:7361-4. 2009
    ..In 42% of HLA-A2 patients following VZV reactivation, these IE62-ALW-A2 T cells could be detected ex vivo...
  28. pmc Induction of A. fumigatus-specific CD4-positive T cells in patients recovering from invasive aspergillosis
    Hetty Jolink
    Department of Hematology, Leiden University Medical Center Department of Infectious Diseases, Leiden University Medical Center
    Haematologica 99:1255-63. 2014
    ..These data indicate that the presence of Aspergillus-specific T cells with a T helper-1 phenotype correlates with the clearance of aspergillus infection. ..
  29. pmc Extracellular domains of CD8α and CD8ß subunits are sufficient for HLA class I restricted helper functions of TCR-engineered CD4(+) T cells
    Marleen M van Loenen
    Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 8:e65212. 2013
    ....
  30. pmc High-throughput identification of potential minor histocompatibility antigens by MHC tetramer-based screening: feasibility and limitations
    Pleun Hombrink
    Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 6:e22523. 2011
    ..However, the high-sensitivity of this approach requires the use of potential epitope sets that are not solely based on MHC binding, to prevent the frequent detection of T-cell responses that lack biological relevance...
  31. ncbi Adult and cord blood T cells can acquire HA-1 specificity through HA-1 T-cell receptor gene transfer
    Bregje Mommaas
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Haematologica 90:1415-21. 2005
    ..This strategy would be particularly useful in case of relapse after cord blood transplantation (CBT) and is explored in this study...
  32. ncbi Impact of peptides on the recognition of HLA class I molecules by human HLA antibodies
    Arend Mulder
    Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 175:5950-7. 2005
    ..Since Abs that are only reactive with HLA loaded with irrelevant peptides are expected to be harmless toward allografts, the practice of HLA Ab determination on lymphocyte-derived HLA deserves reconsideration...
  33. ncbi Defective synthesis or association of T-cell receptor chains underlies loss of surface T-cell receptor-CD3 expression in enteropathy-associated T-cell lymphoma
    Jennifer M L Tjon
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, USA
    Blood 112:5103-10. 2008
    ..Pre)malignant transformation in RCD II thus correlates with defective synthesis or defective association of the TCR chains, resulting in loss of surface TCR-CD3 expression...
  34. pmc Varicellovirus UL 49.5 proteins differentially affect the function of the transporter associated with antigen processing, TAP
    Danijela Koppers-Lalic
    Center of Infectious Diseases and Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands
    PLoS Pathog 4:e1000080. 2008
    ..5. Taken together, these results classify the UL 49.5 gene products of BHV-1, PRV, EHV-1, and EHV-4 as members of a novel family of viral immune evasion proteins, inhibiting TAP through a variety of mechanisms...
  35. ncbi Optimizing TCR gene transfer
    Mirjam H M Heemskerk
    Leiden University Medical Center, Department of Hematology, C2 R, PO Box 9600, 2300 RC, Leiden, The Netherlands
    Clin Immunol 119:121-2. 2006
  36. doi Transcriptional silencing of RFXAP in MHC class II-deficiency
    Marja C J A van Eggermond
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands
    Mol Immunol 45:2920-8. 2008
    ..Together, this insertion in the promoter region represents a novel type of MHC-II gene silencing in MHC-II deficiency patients...
  37. ncbi Mesenchymal stem cells promote engraftment of human umbilical cord blood-derived CD34(+) cells in NOD/SCID mice
    Willy A Noort
    Department of Hematology, Leiden University Medical Center, Leiden University Medical Center, The Netherlands
    Exp Hematol 30:870-8. 2002
    ..In cotransplantation experiments, we examined the homing of MSC as well as the effect on engraftment of human umbilical cord blood (UCB)-derived CD34(+) cells in NOD/SCID mice...
  38. ncbi Functional role of alternatively spliced deoxycytidine kinase in sensitivity to cytarabine of acute myeloid leukemic cells
    Marjan J T Veuger
    Laboratory of Experimental Hematology, Department of Hematology, Leiden University Medical Center, The Netherlands
    Blood 99:1373-80. 2002
    ..However, a cell expressing alternatively spliced dCK forms that has lost wt dCK expression is resistant to the cytotoxic effects of AraC...
  39. pmc Conditional MHC class I ligands and peptide exchange technology for the human MHC gene products HLA-A1, -A3, -A11, and -B7
    Arnold H Bakker
    Divisions of Immunology and Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands
    Proc Natl Acad Sci U S A 105:3825-30. 2008
    ..The conditional ligand technology developed here will allow high-throughput MHC-based analysis of cytotoxic T cell immunity in the vast majority of Western European individuals...
  40. ncbi Functional human antigen-specific T cells produced in vitro using retroviral T cell receptor transfer into hematopoietic progenitors
    Anja U van Lent
    Department of Cell Biology and Histology, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands
    J Immunol 179:4959-68. 2007
    ..Therapeutic applications may arise from these results because they provide a way to produce large numbers of autologous mature Ag-specific T cells in vitro from undifferentiated hemopoietic progenitors...
  41. ncbi Pretransplantation CMV-specific T cells protect recipients of T-cell-depleted grafts against CMV-related complications
    Yves Chalandon
    Division of Hematology, Department of Internal Medicine, University Hospital Geneva, Switzerland
    Blood 107:389-96. 2006
    ..Hence, when a T-cell depletion protocol is used that favors the survival of recipient T cells, the patient's pretransplantation CMV-specific immunity protects against posttransplantation CMV-related complications...
  42. ncbi Strong selection of virus-specific cytotoxic CD4+ T-cell clones during primary human cytomegalovirus infection
    Ester M M van Leeuwen
    Department of Experimental Immunology, Division of Nephrology, Academic Medical Center, Amsterdam, The Netherlands
    Blood 108:3121-7. 2006
    ....
  43. ncbi Designer T cells by T cell receptor replacement
    Daniel Sommermeyer
    Max Delbruck Center for Molecular Medicine, Berlin, Germany
    Eur J Immunol 36:3052-9. 2006
    ....