Cornelis J M Melief

Summary

Affiliation: Leiden University Medical Center
Country: The Netherlands

Publications

  1. doi request reprint Cancer immunotherapy by dendritic cells
    Cornelis J M Melief
    Department of Immunohematology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands ISA Pharmaceuticals, 3723 MB Bilthoven, The Netherlands
    Immunity 29:372-83. 2008
  2. ncbi request reprint Cancer immunology: cat and mouse games
    Cornelis J M Melief
    Nature 437:41-2. 2005
  3. ncbi request reprint Synthesis of 2-alkoxy-8-hydroxyadenylpeptides: towards synthetic epitope-based vaccines
    Jimmy J Weterings
    Leiden Institute of Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands
    Bioorg Med Chem Lett 16:3258-61. 2006
  4. doi request reprint "License to kill" reflects joint action of CD4 and CD8 T cells
    Cornelis J M Melief
    ISA Pharmaceuticals and Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 19:4295-6. 2013
  5. doi request reprint Selective activation of oxygen-deprived tumor-infiltrating lymphocytes through local intratumoral delivery of CD137 monoclonal antibodies
    Cornelis J M Melief
    Immune System Activation, Leiden University Medical Center, Leiden, The Netherlands
    Cancer Discov 2:586-7. 2012
  6. pmc Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses
    R P Sutmuller
    Department of Immunohematology and Blood Transfusion, Tumor Immunology Lab, E3-Q, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    J Exp Med 194:823-32. 2001
  7. ncbi request reprint Mini-review: Regulation of cytotoxic T lymphocyte responses by dendritic cells: peaceful coexistence of cross-priming and direct priming?
    Cornelis J M Melief
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Immunol 33:2645-54. 2003
  8. ncbi request reprint Effective therapeutic anticancer vaccines based on precision guiding of cytolytic T lymphocytes
    Cornelis J M Melief
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    Immunol Rev 188:177-82. 2002
  9. ncbi request reprint Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines
    Cornelis J M Melief
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
    Nat Rev Cancer 8:351-60. 2008
  10. doi request reprint Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine
    Marij J P Welters
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 14:178-87. 2008

Detail Information

Publications94

  1. doi request reprint Cancer immunotherapy by dendritic cells
    Cornelis J M Melief
    Department of Immunohematology, Leiden University Medical Center, 2300 RC Leiden, the Netherlands ISA Pharmaceuticals, 3723 MB Bilthoven, The Netherlands
    Immunity 29:372-83. 2008
    ..Here, I discuss the considerations for generating promising therapeutic antitumor vaccines that use DCs...
  2. ncbi request reprint Cancer immunology: cat and mouse games
    Cornelis J M Melief
    Nature 437:41-2. 2005
  3. ncbi request reprint Synthesis of 2-alkoxy-8-hydroxyadenylpeptides: towards synthetic epitope-based vaccines
    Jimmy J Weterings
    Leiden Institute of Chemistry, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands
    Bioorg Med Chem Lett 16:3258-61. 2006
    ..The immunogenicity of the compounds has been evaluated in IL-12 production and antigen presentation assays...
  4. doi request reprint "License to kill" reflects joint action of CD4 and CD8 T cells
    Cornelis J M Melief
    ISA Pharmaceuticals and Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 19:4295-6. 2013
    ..Synthetic long peptides of KIF20A stimulate synergy between these two T-cell types to promote cancer cell killing...
  5. doi request reprint Selective activation of oxygen-deprived tumor-infiltrating lymphocytes through local intratumoral delivery of CD137 monoclonal antibodies
    Cornelis J M Melief
    Immune System Activation, Leiden University Medical Center, Leiden, The Netherlands
    Cancer Discov 2:586-7. 2012
    ....
  6. pmc Synergism of cytotoxic T lymphocyte-associated antigen 4 blockade and depletion of CD25(+) regulatory T cells in antitumor therapy reveals alternative pathways for suppression of autoreactive cytotoxic T lymphocyte responses
    R P Sutmuller
    Department of Immunohematology and Blood Transfusion, Tumor Immunology Lab, E3-Q, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    J Exp Med 194:823-32. 2001
    ..Simultaneous intervention with both regulatory mechanisms is therefore a promising concept for the induction of therapeutic antitumor immunity...
  7. ncbi request reprint Mini-review: Regulation of cytotoxic T lymphocyte responses by dendritic cells: peaceful coexistence of cross-priming and direct priming?
    Cornelis J M Melief
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Immunol 33:2645-54. 2003
    ..Experiments utilizing DC depletion are needed to further examine the role of processes such as cross-priming and costimulation in the immune response...
  8. ncbi request reprint Effective therapeutic anticancer vaccines based on precision guiding of cytolytic T lymphocytes
    Cornelis J M Melief
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    Immunol Rev 188:177-82. 2002
    ..The recently acquired insights into antigen presentation and costimulatory signals have made possible the development of a new generation of therapeutic anticancer vaccines...
  9. ncbi request reprint Immunotherapy of established (pre)malignant disease by synthetic long peptide vaccines
    Cornelis J M Melief
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
    Nat Rev Cancer 8:351-60. 2008
    ..Proper DC activation then induces the therapeutic CD4+ and CD8+ T-cell responses that are associated with regression of established (pre)malignant lesions, including those induced by high-risk human papilloma virus...
  10. doi request reprint Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine
    Marij J P Welters
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 14:178-87. 2008
    ..The study aims to evaluate the effect of a human papillomavirus type 16 (HPV16) E6 and E7 synthetic long peptides vaccine on the antigen-specific T-cell response in cervical cancer patients...
  11. ncbi request reprint Activation of dendritic cells that cross-present tumor-derived antigen licenses CD8+ CTL to cause tumor eradication
    Geertje J D van Mierlo
    Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 173:6753-9. 2004
    ..Together these results indicate that dendritic cells, depending on their activation state, orchestrate the outcome of CTL-mediated immunity against tumors, leading either to an ineffective immune response or potent antitumor immunity...
  12. ncbi request reprint The tumoricidal activity of memory CD8+ T cells is hampered by persistent systemic antigen, but full functional capacity is regained in an antigen-free environment
    Annemieke Th den Boer
    Department of Immunohematology, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 172:6074-9. 2004
    ....
  13. ncbi request reprint Immune complex-loaded dendritic cells are superior to soluble immune complexes as antitumor vaccine
    Danita H Schuurhuis
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands
    J Immunol 176:4573-80. 2006
    ..These findings show that targeting ICs via the activating Fc gammaRs to DCs in vitro is superior to direct IC vaccination to induce protective tumor immunity in vivo...
  14. ncbi request reprint Multiple CD4 and CD8 T-cell activation parameters predict vaccine efficacy in vivo mediated by individual DC-activating agonists
    Marij J P Welters
    Departments of Immunohematology and Blood Transfusion, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
    Vaccine 25:1379-89. 2007
    ..Importantly, the capacity of an agonist to function as an adjuvant depended on the vaccine strategy used. Collectively, the multi-parameter system presented here can be used as a general road map to develop therapeutic vaccines...
  15. doi request reprint Superior induction of anti-tumor CTL immunity by extended peptide vaccines involves prolonged, DC-focused antigen presentation
    Martijn S Bijker
    Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, Leiden, The Netherlands
    Eur J Immunol 38:1033-42. 2008
    ..An additional advantage of extended CTL peptide vaccines is an increased duration of in vivo epitope presentation...
  16. ncbi request reprint Vaccination against HPV-16 oncoproteins for vulvar intraepithelial neoplasia
    Gemma G Kenter
    Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
    N Engl J Med 361:1838-47. 2009
    ..Spontaneous regression occurs in less than 1.5% of patients, and the rate of recurrence after treatment is high...
  17. ncbi request reprint Macrophages are vital in spontaneous intraocular tumor eradication
    Zita F H M Boonman
    Department of Ophthalmology, Leiden University Medical Center, The Netherlands
    Invest Ophthalmol Vis Sci 47:2959-65. 2006
    ..This study was conducted to determine whether macrophages are involved in the natural elimination of this intraocular tumor...
  18. ncbi request reprint Intraocular tumor antigen drains specifically to submandibular lymph nodes, resulting in an abortive cytotoxic T cell reaction
    Zita F H M Boonman
    Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 172:1567-74. 2004
    ..However, the induced tumor-specific immunity is insufficient for tumor clearance, even combined with otherwise highly effective immune intervention protocols...
  19. ncbi request reprint Antigen presentation by an immature myeloid dendritic cell line does not cause CTL deletion in vivo, but generates CD8+ central memory-like T cells that can be rescued for full effector function
    Hélène Dumortier
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    J Immunol 175:855-63. 2005
    ....
  20. ncbi request reprint Characterization of antigen-specific immune responses induced by canarypox virus vaccines
    Rinke Bos
    Department of Immunohematology and Blood Transfusion, Tumor Immunology Group, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 179:6115-22. 2007
    ..This consideration needs to be taken into account with respect to the design and evaluation of vaccination strategies that use ALVAC-based vaccine...
  21. ncbi request reprint Frequent display of human papillomavirus type 16 E6-specific memory t-Helper cells in the healthy population as witness of previous viral encounter
    Marij J P Welters
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
    Cancer Res 63:636-41. 2003
    ....
  22. ncbi request reprint Human papillomavirus type 16-positive cervical cancer is associated with impaired CD4+ T-cell immunity against early antigens E2 and E6
    Annemieke de Jong
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Cancer Res 64:5449-55. 2004
    ..Therefore, our observations concerning the lack of functional HPV16-specific CD4+ T-cell immunity in patients with cervical cancer offer a possible explanation for the development of this disease...
  23. pmc Success or failure of vaccination for HPV16-positive vulvar lesions correlates with kinetics and phenotype of induced T-cell responses
    Marij J P Welters
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
    Proc Natl Acad Sci U S A 107:11895-9. 2010
    ..Foxp3(+) T cells have been associated previously with impaired immunity in malignancies. Here we demonstrate that the vaccine-prompted level of this population is associated with early treatment failure...
  24. doi request reprint DC-induced CD8(+) T-cell response is inhibited by MHC class II-dependent DX5(+)CD4(+) Treg
    Wanda G H Han
    Department of Rheumatology, Leiden University Medical Center, The Netherlands
    Eur J Immunol 39:1765-73. 2009
    ..Together, our data show an inhibitory role of CD4(+) T cells on the induction of CD8(+) T-cell responses by activated DC and indicate the involvement of DX5(+)CD4(+), but not CD4(+)CD25(+), T cells in this process...
  25. ncbi request reprint Prediction of the immunogenic potential of frameshift-mutated antigens in microsatellite instable cancer
    Frank M Speetjens
    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
    Int J Cancer 123:838-45. 2008
    ....
  26. ncbi request reprint CD8+ CTL priming by exact peptide epitopes in incomplete Freund's adjuvant induces a vanishing CTL response, whereas long peptides induce sustained CTL reactivity
    Martijn S Bijker
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, The Netherlands
    J Immunol 179:5033-40. 2007
    ....
  27. ncbi request reprint Established human papillomavirus type 16-expressing tumors are effectively eradicated following vaccination with long peptides
    Sander Zwaveling
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 169:350-8. 2002
    ..Because the vaccine types used in this study are easy to prepare under good manufacturing practice conditions and are safe to administer to humans, these data provide important information for future clinical trials...
  28. ncbi request reprint Distinct regulation and impact of type 1 T-cell immunity against HPV16 L1, E2 and E6 antigens during HPV16-induced cervical infection and neoplasia
    Mariette I E van Poelgeest
    Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
    Int J Cancer 118:675-83. 2006
    ..This argues that T-cell responses against early and late HPV16 antigens essentially differ in the manner in which they are induced and regulated, as well as in their impact on the subsequent stages of HPV16-induced cervical disease...
  29. ncbi request reprint Distinct uptake mechanisms but similar intracellular processing of two different toll-like receptor ligand-peptide conjugates in dendritic cells
    Selina Khan
    Department of Immunohematology and Blood Transfusion, Molecular Cell Biology, and Clinical Oncology, Leiden University Medical Centre, P O Box 9600, 2300 RC Leiden, The Netherlands
    J Biol Chem 282:21145-59. 2007
    ..Together, our data show that targeting to two distinct TLRs requires distinct uptake mechanism but follows similar trafficking and intracellular processing pathways leading to optimal antigen presentation and T-cell priming...
  30. ncbi request reprint Rapid enrichment of human papillomavirus (HPV)-specific polyclonal T cell populations for adoptive immunotherapy of cervical cancer
    Annemieke de Jong
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Building 1 E3 Q, 2300 RC Leiden, The Netherlands
    Int J Cancer 114:274-82. 2005
    ..These HPV16E6-specific CD4(+) T cells may turn out to be an essential component of future adoptive T cell therapy for advanced cervical cancer, by orchestrating CTL dependent and independent tumoricidal mechanisms...
  31. doi request reprint Peptide vaccination after T-cell transfer causes massive clonal expansion, tumor eradication, and manageable cytokine storm
    Long V Ly
    Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands
    Cancer Res 70:8339-46. 2010
    ..Together, these results identify a peptide vaccination strategy that can potently accentuate effective ACT in non-lymphodepleted hosts...
  32. doi request reprint Phase I immunotherapeutic trial with long peptides spanning the E6 and E7 sequences of high-risk human papillomavirus 16 in end-stage cervical cancer patients shows low toxicity and robust immunogenicity
    Gemma G Kenter
    Department of Gynaecology, Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 14:169-77. 2008
    ..To determine the toxicity, safety, and immunogenicity of a human papillomavirus 16 (HPV16) E6 and E7 long peptide vaccine administered to end-stage cervical cancer patients...
  33. ncbi request reprint Selective cytotoxic T-lymphocyte targeting of tumor immune escape variants
    Thorbald van Hall
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
    Nat Med 12:417-24. 2006
    ..This explains why they act as immunogenic neoantigens. The newly discovered epitopes can be exploited for immune intervention against processing-deficient tumors through adoptive T-cell transfer or peptide vaccination...
  34. doi request reprint Reduced human leukocyte antigen expression in advanced-stage Ewing sarcoma: implications for immune recognition
    Dagmar Berghuis
    Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
    J Pathol 218:222-31. 2009
    ..The majority of EWS tumours, particularly if advanced-stage, exhibit complete or partial absence of both classes of HLA. This knowledge will be instrumental in the design of cellular immunotherapeutic strategies for advanced-stage EWS...
  35. ncbi request reprint Chemically synthesized protein as tumour-specific vaccine: immunogenicity and efficacy of synthetic HPV16 E7 in the TC-1 mouse tumour model
    Marij J P Welters
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, P O Box 9600, 2300 RC Leiden, The Netherlands
    Vaccine 23:305-11. 2004
    ..Our results demonstrate the potential use of pure synthetic vaccines that can be efficiently produced under GMP at low cost, which will stimulate the translation of new vaccination strategies into phase I/II clinical trials...
  36. pmc A placebo-controlled randomized HPV16 synthetic long-peptide vaccination study in women with high-grade cervical squamous intraepithelial lesions
    Peggy J De Vos Van Steenwijk
    Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
    Cancer Immunol Immunother 61:1485-92. 2012
    ..Thus, vaccination of HSIL patients results in increased HPV16-specific T-cell immunity. Further development of this type of treatment relies on the ability to motivate patients and in the reduction in the side effects...
  37. ncbi request reprint CD4+ T cells are able to promote tumor growth through inhibition of tumor-specific CD8+ T-cell responses in tumor-bearing hosts
    Annemieke Th den Boer
    Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands
    Cancer Res 65:6984-9. 2005
    ..These observations are important for the development of immune interventions aiming at treatment of cancer...
  38. ncbi request reprint Detection of human papillomavirus type 18 E6 and E7-specific CD4+ T-helper 1 immunity in relation to health versus disease
    Marij J P Welters
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, The Netherlands
    Int J Cancer 118:950-6. 2006
    ....
  39. doi request reprint Self-tolerance does not restrict the CD4+ T-helper response against the p53 tumor antigen
    Marjolein M Lauwen
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Cancer Res 68:893-900. 2008
    ..Our findings imply that the p53-specific CD4+ T-cell repertoire is not restricted by self-tolerance and is fully available for the targeting of cancer...
  40. ncbi request reprint Skin reactions to human papillomavirus (HPV) 16 specific antigens intradermally injected in healthy subjects and patients with cervical neoplasia
    Muriel van den Hende
    Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
    Int J Cancer 123:146-52. 2008
    ....
  41. ncbi request reprint Antitumor efficacy of wild-type p53-specific CD4(+) T-helper cells
    Sander Zwaveling
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands
    Cancer Res 62:6187-93. 2002
    ..Therefore, exploitation of the p53-specific Th response appears to be a highly useful aspect of immunotherapeutic strategies against cancers...
  42. doi request reprint Dendritic cells process synthetic long peptides better than whole protein, improving antigen presentation and T-cell activation
    Rodney A Rosalia
    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Immunol 43:2554-65. 2013
    ....
  43. ncbi request reprint Human papilloma virus specific T cells infiltrating cervical cancer and draining lymph nodes show remarkably frequent use of HLA-DQ and -DP as a restriction element
    Sytse J Piersma
    Department of Clinical Oncology, Leiden University Medical Center, 2333 ZA, Leiden, The Netherlands
    Int J Cancer 122:486-94. 2008
    ..This is crucial for the optimization of cancer immunotherapy in patients with pre-existing tumor-immunity...
  44. ncbi request reprint Detection and functional analysis of CD8+ T cells specific for PRAME: a target for T-cell therapy
    Marieke Griffioen
    Department of Clinical Oncology, Leiden University Medical Center, Leiden, Netherlands
    Clin Cancer Res 12:3130-6. 2006
    ..The purpose of this study is to investigate the usefulness of PRAME as target for anticancer T-cell therapies...
  45. doi request reprint Evaluation of immunological cross-reactivity between clade A9 high-risk human papillomavirus types on the basis of E6-Specific CD4+ memory T cell responses
    Muriel van den Hende
    Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
    J Infect Dis 202:1200-11. 2010
    ..Our data indicate that natural and vaccine-induced HPV16 E6-specific CD4(+) T cell responses are unlikely to mediate efficient cross-protection against other clade A9 members...
  46. doi request reprint Induction of p53-specific immunity by a p53 synthetic long peptide vaccine in patients treated for metastatic colorectal cancer
    Frank M Speetjens
    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 15:1086-95. 2009
    ..The safety and immunogenicity of a p53 synthetic long peptide (p53-SLP) vaccine were investigated in patients treated for metastatic colorectal cancer...
  47. ncbi request reprint Immunotherapy of cancer through targeting of the p53 tumor antigen
    Sander Zwaveling
    Leiden University Medical Center, Department of Immunohematology and Blood Transfusion, Tumor Immunology Group, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    Arch Immunol Ther Exp (Warsz) 50:297-305. 2002
    ..However, potential complications as a result of immunological tolerance or autoimmune pathology must be taken into account when exploiting this ubiquitously expressed auto-antigen for the immunotherapy of cancer...
  48. ncbi request reprint Improved peptide vaccine strategies, creating synthetic artificial infections to maximize immune efficacy
    Sjoerd H van der Burg
    Department of Clinical Oncology, Leiden University Medical Centre, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    Adv Drug Deliv Rev 58:916-30. 2006
    ..In this article we review the key changes in the design, formulation and delivery of synthetic peptide vaccines that are applied to improve peptide vaccine strategies...
  49. pmc HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial
    Mariette I E van Poelgeest
    Department of Gynaecology, Leiden University Medical Center, Leiden, The Netherlands
    J Transl Med 11:88. 2013
    ..Here, we determined the toxicity, safety, immunogenicity and efficacy of the HPV16 SLP vaccine in patients with advanced or recurrent HPV16-induced gynecological carcinoma...
  50. ncbi request reprint Magnitude and polarization of P53-specific T-helper immunity in connection to leukocyte infiltration of colorectal tumors
    Sjoerd H van der Burg
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Int J Cancer 107:425-33. 2003
    ....
  51. doi request reprint Competition-based cellular peptide binding assay for HLA class I
    Jan H Kessler
    Leiden University Medical Center, Leiden, Netherlands
    Curr Protoc Immunol . 2004
    ..It can be performed in a normally equipped cellular laboratory, requires no additional equipment besides a flow cytometer (FACS), and is relatively easy to perform. Assay-specific parameters for several HLA alleles are provided...
  52. ncbi request reprint High number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancer
    Sytse J Piersma
    Department of Clinical Oncology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Cancer Res 67:354-61. 2007
    ..Our data indicate that, especially in a subgroup of LN- patients, a strong and effective interaction between immune system and tumor exists. This subgroup of cervical cancer patients may have the best prognosis...
  53. ncbi request reprint Effective CD8(+) T cell priming and tumor protection by enterotoxin B subunit-conjugated peptides targeted to dendritic cells
    Nathalie Fu
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Vaccine 27:5252-8. 2009
    ..Our data demonstrate that bacterial non-toxic B subunit-peptide conjugates are potent vaccine vehicles for induction of protective CD8(+) T cell responses...
  54. ncbi request reprint Design and development of synthetic peptide vaccines: past, present and future
    Martijn S Bijker
    Leiden University Medical Center, Department of Immunohematology, Leiden, The Netherlands
    Expert Rev Vaccines 6:591-603. 2007
    ..The current state-of-the-art peptide vaccine is a complete synthetic inflammatory product that is ingested by professional antigen-presenting cells and stimulates both CD4(+) and CD8(+) T cells...
  55. pmc Association of cervical cancer with the presence of CD4+ regulatory T cells specific for human papillomavirus antigens
    Sjoerd H van der Burg
    Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
    Proc Natl Acad Sci U S A 104:12087-92. 2007
    ..Our findings offer a plausible explanation for the observed failure of the tumor-specific immune response in patients with cervical carcinoma...
  56. ncbi request reprint IgG-mediated anaphylaxis to a synthetic long peptide vaccine containing a B cell epitope can be avoided by slow-release formulation
    Esther D Quakkelaar
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
    J Immunol 192:5813-20. 2014
    ..This study underscores both the immunogenicity of SLP vaccination, for inducing T cell as well as B cell responses, and the necessity of safe administration routes. ..
  57. ncbi request reprint Detection of human papillomavirus (HPV) 16-specific CD4+ T-cell immunity in patients with persistent HPV16-induced vulvar intraepithelial neoplasia in relation to clinical impact of imiquimod treatment
    Mariette I E van Poelgeest
    Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 11:5273-80. 2005
    ..We have charted HPV16-specific immunity in 29 patients with high-grade VIN and examined its role in the clinical effect of imiquimod treatment...
  58. doi request reprint Addition of interferon-α to the p53-SLP® vaccine results in increased production of interferon-γ in vaccinated colorectal cancer patients: a phase I/II clinical trial
    Eliane C M Zeestraten
    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
    Int J Cancer 132:1581-91. 2013
    ..When compared to a similar trial with p53-SLP® vaccination alone the combination was found to induce significantly more IFN-γ producing p53-specific T cells...
  59. pmc The simultaneous ex vivo detection of low-frequency antigen-specific CD4+ and CD8+ T-cell responses using overlapping peptide pools
    Satwinder Kaur Singh
    Department of Clinical Oncology, Building 1, K1 P, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
    Cancer Immunol Immunother 61:1953-63. 2012
    ....
  60. ncbi request reprint In vivo triggering through 4-1BB enables Th-independent priming of CTL in the presence of an intact CD28 costimulatory pathway
    Linda Diehl
    Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 168:3755-62. 2002
    ..The powerful effects of 4-1BB triggering on the induction, amplification, and persistence of CTL responses provide a novel strategy for increasing the potency of vaccines against cancers...
  61. ncbi request reprint NK cells recognize and lyse Ewing sarcoma cells through NKG2D and DNAM-1 receptor dependent pathways
    Dirk H J Verhoeven
    Division of Immunology, Hematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Department of Pediatrics, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
    Mol Immunol 45:3917-25. 2008
    ..To explore the feasibility of natural killer (NK) cell mediated immunotherapy and to identify molecular mechanisms involved, the susceptibility of EWS to NK cells was investigated...
  62. ncbi request reprint Differential expression regulation of the alpha and beta subunits of the PA28 proteasome activator in mature dendritic cells
    Ferry Ossendorp
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    J Immunol 174:7815-22. 2005
    ..Therefore, maturation of DC not only improves costimulation but also MHC class I processing. This mechanism enhances the CD8(+) CTL (cross)-priming capacity of mature DC...
  63. ncbi request reprint CD25+ cell depletion hastens the onset of severe disease in collagen-induced arthritis
    Mary E Morgan
    Leiden University Medical Center, Leiden, The Netherlands
    Arthritis Rheum 48:1452-60. 2003
    ..We wished to evaluate their potential for influencing systemic and chronic joint inflammation by investigating their involvement in collagen-induced arthritis (CIA)...
  64. ncbi request reprint Prognostic value of tumor-infiltrating dendritic cells in colorectal cancer: role of maturation status and intratumoral localization
    Maro H Sandel
    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 11:2576-82. 2005
    ..03). We found that tumor-infiltrating dendritic cells had preferential infiltration sites within a tumor, affected local tumor cell-immune cell interactions, and correlated to the clinical prognosis of colorectal cancer patients...
  65. pmc Improved innate and adaptive immunostimulation by genetically modified HIV-1 protein expressing NYVAC vectors
    Esther D Quakkelaar
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    PLoS ONE 6:e16819. 2011
    ..This combined replication-competent NYVAC is a promising candidate for the next generation of HIV vaccines...
  66. doi request reprint Balancing between antitumor efficacy and autoimmune pathology in T-cell-mediated targeting of carcinoembryonic antigen
    Rinke Bos
    Department of Immunohematology and Blood Transfusion, Tumor Immunology Group, Leiden University Medical Center, Leiden, The Netherlands
    Cancer Res 68:8446-55. 2008
    ....
  67. ncbi request reprint Chirality of TLR-2 ligand Pam3CysSK4 in fully synthetic peptide conjugates critically influences the induction of specific CD8+ T-cells
    Selina Khan
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands
    Mol Immunol 46:1084-91. 2009
    ..In summary we show that the favourable effects of the Pam(R)-configuration of TLR-2 ligand can be attributed to direct effects on dendritic cells resulting in enhancement of CD8(+) T-cell responses...
  68. ncbi request reprint The status of HPV16-specific T-cell reactivity in health and disease as a guide to HPV vaccine development
    Sjoerd H van der Burg
    Tumor Immunology Group, Department of Immunohematology and Blood Transfusion, University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands
    Virus Res 89:275-84. 2002
    ....
  69. ncbi request reprint Vaccine-induced effector-memory CD8+ T cell responses predict therapeutic efficacy against tumors
    Suzanne van Duikeren
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
    J Immunol 189:3397-403. 2012
    ..c. tumors. Thus, characteristics of vaccine-induced CD8(+) T cell responses instill a predictive determinant for the efficacy of vaccines during tumor therapy...
  70. ncbi request reprint Circulating specific antibodies enhance systemic cross-priming by delivery of complexed antigen to dendritic cells in vivo
    Nadine van Montfoort
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Immunol 42:598-606. 2012
    ..These findings have important implications for the understanding of the action of therapeutic antibodies against tumor-associated antigens intensively used in the clinic nowadays...
  71. ncbi request reprint Tumor-expressed B7-H1 and B7-DC in relation to PD-1+ T-cell infiltration and survival of patients with cervical carcinoma
    Rezaul Karim
    Departments of Center for Human and Clinical Genetics, Immunohematology and Blood Transfusion, Clinical Oncology, Pathology, and Gynecology, Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 15:6341-7. 2009
    ..The aim of this study was to determine B7-H1, B7-DC, and PD-1 expression in cervical carcinoma...
  72. doi request reprint 2-Azidoalkoxy-7-hydro-8-oxoadenine derivatives as TLR7 agonists inducing dendritic cell maturation
    Jimmy J Weterings
    Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands
    Bioorg Med Chem Lett 19:2249-51. 2009
    ..The synthesis of an array of 2-azidoalkoxy substituted 7-hydro-8-oxoadenines is described. The relation of the structure of these compounds and their ability to induce maturation of dendritic cells is evaluated...
  73. ncbi request reprint Recombinant adenovirus-transduced human dendritic cells engineered to secrete interleukin-10 (IL-10) suppress Th1-type responses while selectively activating IL-10-producing CD4+ T cells
    Delphine Rea
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Hum Immunol 65:1344-55. 2004
    ..Our data argue that rAd-infected human DCs genetically engineered to produce IL-10 may be exploited for the modulation of harmful Th1-type responses in transplantation and autoimmune diseases...
  74. doi request reprint Antigen processing by nardilysin and thimet oligopeptidase generates cytotoxic T cell epitopes
    Jan H Kessler
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
    Nat Immunol 12:45-53. 2011
    ..By broadening the antigenic peptide repertoire, nardilysin and TOP strengthen the immune defense against intracellular pathogens and cancer...
  75. ncbi request reprint Competition-based cellular peptide binding assays for 13 prevalent HLA class I alleles using fluorescein-labeled synthetic peptides
    Jan H Kessler
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands
    Hum Immunol 64:245-55. 2003
    ..Thus these convenient and accurate peptide-binding assays will be useful for the identification of putative cytotoxic T lymphocyte epitopes presented on a diverse array of HLA class I molecules...
  76. ncbi request reprint Safety of intravenous administration of a canarypox virus encoding the human wild-type p53 gene in colorectal cancer patients
    Anand G Menon
    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
    Cancer Gene Ther 10:509-17. 2003
    ..All other patients showed progressive disease. We conclude that ALVAC-p53 can be administered intravenously to colorectal cancer patients without serious toxicity or pathological autoimmunity and can induce immune responses against p53...
  77. ncbi request reprint Antigen-antibody immune complexes empower dendritic cells to efficiently prime specific CD8+ CTL responses in vivo
    Danita H Schuurhuis
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands
    J Immunol 168:2240-6. 2002
    ..quot; These findings indicate that the presence of specific Abs can crucially affect the induction of cytotoxic cellular responses...
  78. doi request reprint The detection of circulating human papillomavirus-specific T cells is associated with improved survival of patients with deeply infiltrating tumors
    Moniek Heusinkveld
    Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
    Int J Cancer 128:379-89. 2011
    ....
  79. ncbi request reprint Frequent detection of human papillomavirus 16 E2-specific T-helper immunity in healthy subjects
    Annemieke de Jong
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Cancer Res 62:472-9. 2002
    ....
  80. pmc CD40 stimulation leads to effective therapy of CD40(-) tumors through induction of strong systemic cytotoxic T lymphocyte immunity
    Geertje J D van Mierlo
    Department of Immunohematology and Bloodtransfusion, Leiden University Medical Center, P O Box 9600, 2300 RC, Leiden, The Netherlands
    Proc Natl Acad Sci U S A 99:5561-6. 2002
    ..Our data indicate that the immune response after cancer-host interactions can be directed toward competence, leading to the cure of established tumors merely by delivery of a CD40-dependent "license to kill" signal...
  81. ncbi request reprint SPI-CI and SPI-6 cooperate in the protection from effector cell-mediated cytotoxicity
    Michael Bots
    Department of Clinical Oncology, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC, Leiden, The Netherlands
    Blood 105:1153-61. 2005
    ..Our data therefore indicate that SPI-CI is a novel immune escape molecule that acts in concert with SPI-6 to prevent cytotoxic lymphocyte-mediated killing of tumor cells...
  82. ncbi request reprint Expression of a natural tumor antigen by thymic epithelial cells impairs the tumor-protective CD4+ T-cell repertoire
    Rinke Bos
    Department of Immunohematology and Blood Transfusion, Tumor Immunology Group, Leiden University Medical Center, Leiden, Netherlands
    Cancer Res 65:6443-9. 2005
    ....
  83. ncbi request reprint Induction of p53-specific immune responses in colorectal cancer patients receiving a recombinant ALVAC-p53 candidate vaccine
    Sjoerd H van der Burg
    Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands
    Clin Cancer Res 8:1019-27. 2002
    ..Experiments in preclinical models have shown that it can serve as a target for T-cell-mediated tumor-eradication. The feasibility of a p53-specific therapeutic vaccination was investigated in cancer patients...
  84. pmc Enhancement of proliferation and downregulation of TRAIL expression on CD8+ T cells by IL-21
    Cornelis J M Melief
    Department of Immunohematology, Leiden University Medical Center, Leiden, The Netherlands
    Eur J Immunol 40:2990-2. 2010
    ..This finding helps to define the role of IL-21 in the CD8 response, and raises new questions relevant for achieving a broader understanding of this multifunctional cytokine...
  85. ncbi request reprint CD8 T-cell recognition of human 5T4 oncofetal antigen
    Lucy J C Smyth
    Immunology Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom
    Int J Cancer 119:1638-47. 2006
    ..In conclusion, there is a repertoire of CD8 T cell recognition of 5T4 in normal human donors and some candidate HLA-A*0201 epitopes have been identified...
  86. ncbi request reprint Differential kinetics of antigen-specific CD4+ and CD8+ T cell responses in the regression of retrovirus-induced sarcomas
    Koen Schepers
    Department of Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
    J Immunol 169:3191-9. 2002
    ....
  87. pmc Spontaneous tumor rejection by cbl-b-deficient CD8+ T cells
    Stefanie Loeser
    Institute of Molecular Biotechnology, Austrian Academy of Science, 1030 Vienna, Austria
    J Exp Med 204:879-91. 2007
    ..Inhibition of Cbl-b is a novel approach to stimulate long-lasting immunity against cancer...
  88. ncbi request reprint Escort service for cross-priming
    Cornelis J M Melief
    Nat Immunol 6:543-4. 2005
  89. ncbi request reprint Dendritic cell immunotherapy: mapping the way
    Carl G Figdor
    Department of Tumor Immunology, Nijmegen Center for Molecular Life Sciences, University Medical Center Nijmegen, PO Box 9101, 6500HB Nijmegen, The Netherlands
    Nat Med 10:475-80. 2004
    ..Although early clinical trials indicate that DC vaccines can induce immune responses in some cancer patients, careful study design and use of standardized clinical and immunological criteria are needed...
  90. ncbi request reprint Expression of cellular FLICE inhibitory protein, caspase-8, and protease inhibitor-9 in Ewing sarcoma and implications for susceptibility to cytotoxic pathways
    Alfons S K de Hooge
    Department of Pediatrics, Division of Immunology, Haematology, Oncology, Bone Marrow Transplantation and Autoimmune Diseases, Leiden University Medical Center, Leiden, The Netherlands
    Clin Cancer Res 13:206-14. 2007
    ..Here, we have studied their in vitro and in vivo expression in Ewing sarcoma and the implications for susceptibility to cytotoxicity...
  91. ncbi request reprint Effective immunotherapy of cancer in MUC1-transgenic mice using clonal cytotoxic T lymphocytes directed against an immunodominant MUC1 epitope
    Lukas C Heukamp
    Imperial Cancer Research Fund, Breast Cancer Biology Group, Guy s Hospital, London, United Kingdom
    J Immunother 25:46-56. 2002
    ....
  92. ncbi request reprint Maintenance of immune tolerance depends on normal tissue homeostasis
    Zita F H M Boonman
    Department of Ophthalmology
    J Immunol 175:4247-54. 2005
    ..These data also indicate that tissue injury in the absence of viral or microbial infection can act as a switch for the induction of CTL immunity...
  93. ncbi request reprint Revival of the regulatory T cell: new targets for drug development
    Roger P M Sutmuller
    Department of Tumor Immunology, NCMLS University Medical Center, Post Box 9101 6500HB, Nijmegen, The Netherlands
    Drug Discov Today 9:310-6. 2004
    ..From our growing knowledge of the field of immunology, we could potentially generate a new class of therapeutic agents that target immune-related diseases...
  94. ncbi request reprint Cancer: immune pact with the enemy
    Cornelis J M Melief
    Nature 450:803-4. 2007