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. 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
  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. 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
  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

Publications46

  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. 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...
  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. 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
    ....
  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. 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...
  16. doi 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...
  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 Identification of Biological Relevant Minor Histocompatibility Antigens within the B-lymphocyte-Derived HLA-Ligandome Using a Reverse Immunology Approach
    Pleun Hombrink
    Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 21:2177-86. 2015
    ....
  19. 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
    ....
  20. 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...
  21. 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...
  22. 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...
  23. doi Therapeutic targeting of the BCR-associated protein CD79b in a TCR-based approach is hampered by aberrant expression of CD79b
    Lorenz Jahn
    Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands
    Blood 125:949-58. 2015
    ..Therefore, aberrant gene expression must be taken into consideration when selecting common, apparently lineage-specific self-antigens as targets for TCR-based immunotherapies. ..
  24. 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...
  25. 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...
  26. 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...
  27. 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
    ....
  28. 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
    ....
  29. 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...
  30. doi Accurate quantitation of MHC-bound peptides by application of isotopically labeled peptide MHC complexes
    Chopie Hassan
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    J Proteomics 109:240-4. 2014
    ..The strategy presented here can be used to obtain a reliable view of epitope copy number and thus allows improvement of vaccine design and strategies for immunotherapy...
  31. 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. ..
  32. 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
    ....
  33. 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...
  34. 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...
  35. 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...
  36. doi 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...
  37. 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...
  38. 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
  39. 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...
  40. 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...
  41. 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...
  42. 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...
  43. 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...
  44. 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...
  45. 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
    ....
  46. 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
    ....