4 results on '"Schaap, Nicolaas P. M."'
Search Results
2. Human CD34+-derived complete plasmacytoid and conventional dendritic cell vaccine effectively induces antigen-specific CD8+ T cell and NK cell responses in vitro and in vivo.
- Author
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van Eck van der Sluijs, Jesper, van Ens, Diede, Brummelman, Jolanda, Heister, Daan, Sareen, Aastha, Truijen, Lisa, van Ingen Schenau, Dorette S., Heemskerk, Mirjam H. M., Griffioen, Marieke, Kester, Michel G. D., Schaap, Nicolaas P. M., Jansen, Joop H., van der Waart, Anniek B., Dolstra, Harry, and Hobo, Willemijn
- Abstract
Allogeneic stem cell transplantation (alloSCT) can be curative for hemato-oncology patients due to effective graft-versus-tumor immunity. However, relapse remains the major cause of treatment failure, emphasizing the need for adjuvant immunotherapies. In this regard, post-transplantation dendritic cell (DC) vaccination is a highly interesting strategy to boost graft-versus-tumor responses. Previously, we developed a clinically applicable protocol for simultaneous large-scale generation of end-stage blood DC subsets from donor-derived CD34
+ stem cells, including conventional type 1 and 2 DCs (cDC1s and cDC2s), and plasmacytoid DCs (pDCs). In addition, the total cultured end-product (DC-complete vaccine), also contains non-end-stage-DCs (i.e. non-DCs). In this study, we aimed to dissect the phenotypic identity of these non-DCs and their potential immune modulatory functions on the potency of cDCs and pDCs in stimulating tumor-reactive CD8+ T and NK cell responses, in order to obtain rationale for clinical translation of our DC-complete vaccine. The non-DC compartment was heterogeneous and comprised of myeloid progenitors and (immature) granulocyte- and monocyte-like cells. Importantly, non-DCs potentiated toll-like receptor-induced DC maturation, as reflected by increased expression of co-stimulatory molecules and enhanced cDC-derived IL-12 and pDC-derived IFN-α production. Additionally, antigen-specific CD8+ T cells effectively expanded upon DC-complete vaccination in vitro and in vivo. This effect was strongly augmented by non-DCs in an antigen-independent manner. Moreover, non-DCs did not impair in vitro DC-mediated NK cell activation, degranulation nor cytotoxicity. Notably, in vivo i.p. DC-complete vaccination activated i.v. injected NK cells. Together, these data demonstrate that the non-DC compartment potentiates DC-mediated activation and expansion of antigen-specific CD8+ T cells and do not impair NK cell responses in vitro and in vivo. This underscores the rationale for further clinical translation of our CD34+ -derived DC-complete vaccine in hemato-oncology patients post alloSCT. [ABSTRACT FROM AUTHOR]- Published
- 2023
- Full Text
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3. Clinically applicable CD34+-derived blood dendritic cell subsets exhibit key subset-specific features and potently boost anti-tumor T and NK cell responses
- Author
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van Eck van der Sluijs, Jesper, van Ens, Diede, Thordardottir, Soley, Vodegel, Denise, Hermens, Inge, van der Waart, Anniek B., Falkenburg, J. H. Frederik, Kester, Michel G. D., de Rink, Iris, Heemskerk, Mirjam H. M., Borst, Jannie, Schaap, Nicolaas P. M., Jansen, Joop H., Xiao, Yanling, Dolstra, Harry, and Hobo, Willemijn
- Subjects
CD34+ hematopoietic progenitor cells ,Cancer Research ,T-Lymphocytes ,Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2] ,medicine.medical_treatment ,Immunology ,Cell ,Cell Culture Techniques ,T cells ,CD34 ,Antigens, CD34 ,CD34(+) hematopoietic progenitor cells ,NK cells ,Biology ,Lymphocyte Activation ,Dendritic cells ,03 medical and health sciences ,Cross-Priming ,0302 clinical medicine ,Immunity ,medicine ,Humans ,Immunology and Allergy ,030304 developmental biology ,Antigen Presentation ,0303 health sciences ,Vaccination ,Dendritic cell ,Immunotherapy ,Hematopoietic Stem Cells ,Acquired immune system ,Clinical application ,Killer Cells, Natural ,Transplantation ,medicine.anatomical_structure ,Oncology ,Cancer research ,Original Article ,Stem cell ,030215 immunology - Abstract
Allogeneic stem cell transplantation (alloSCT), following induction chemotherapy, can be curative for hemato-oncology patients due to powerful graft-versus-tumor immunity. However, disease recurrence remains the major cause of treatment failure, emphasizing the need for potent adjuvant immunotherapy. In this regard, dendritic cell (DC) vaccination is highly attractive, as DCs are the key orchestrators of innate and adaptive immunity. Natural DC subsets are postulated to be more powerful compared with monocyte-derived DCs, due to their unique functional properties and cross-talk capacity. Yet, obtaining sufficient numbers of natural DCs, particularly type 1 conventional DCs (cDC1s), is challenging due to low frequencies in human blood. We developed a clinically applicable culture protocol using donor-derived G-CSF mobilized CD34+ hematopoietic progenitor cells (HPCs) for simultaneous generation of high numbers of cDC1s, cDC2s and plasmacytoid DCs (pDCs). Transcriptomic analyses demonstrated that these ex vivo-generated DCs highly resemble their in vivo blood counterparts. In more detail, we demonstrated that the CD141+CLEG9A+ cDC1 subset exhibited key features of in vivo cDC1s, reflected by high expression of co-stimulatory molecules and release of IL-12p70 and TNF-α. Furthermore, cDC1s efficiently primed alloreactive T cells, potently cross-presented long-peptides and boosted expansion of minor histocompatibility antigen-experienced T cells. Moreover, they strongly enhanced NK cell activation, degranulation and anti-leukemic reactivity. Together, we developed a robust culture protocol to generate highly functional blood DC subsets for in vivo application as tailored adjuvant immunotherapy to boost innate and adaptive anti-tumor immunity in alloSCT patients.
- Published
- 2021
4. Clinically applicable CD34+-derived blood dendritic cell subsets exhibit key subset-specific features and potently boost anti-tumor T and NK cell responses.
- Author
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van Eck van der Sluijs, Jesper, van Ens, Diede, Thordardottir, Soley, Vodegel, Denise, Hermens, Inge, van der Waart, Anniek B., Falkenburg, J. H. Frederik, Kester, Michel G. D., de Rink, Iris, Heemskerk, Mirjam H. M., Borst, Jannie, Schaap, Nicolaas P. M., Jansen, Joop H., Xiao, Yanling, Dolstra, Harry, and Hobo, Willemijn
- Subjects
KILLER cells ,BLOOD cells ,DENDRITIC cells ,T cells ,PROGENITOR cells - Abstract
Allogeneic stem cell transplantation (alloSCT), following induction chemotherapy, can be curative for hemato-oncology patients due to powerful graft-versus-tumor immunity. However, disease recurrence remains the major cause of treatment failure, emphasizing the need for potent adjuvant immunotherapy. In this regard, dendritic cell (DC) vaccination is highly attractive, as DCs are the key orchestrators of innate and adaptive immunity. Natural DC subsets are postulated to be more powerful compared with monocyte-derived DCs, due to their unique functional properties and cross-talk capacity. Yet, obtaining sufficient numbers of natural DCs, particularly type 1 conventional DCs (cDC1s), is challenging due to low frequencies in human blood. We developed a clinically applicable culture protocol using donor-derived G-CSF mobilized CD34
+ hematopoietic progenitor cells (HPCs) for simultaneous generation of high numbers of cDC1s, cDC2s and plasmacytoid DCs (pDCs). Transcriptomic analyses demonstrated that these ex vivo-generated DCs highly resemble their in vivo blood counterparts. In more detail, we demonstrated that the CD141+ CLEG9A+ cDC1 subset exhibited key features of in vivo cDC1s, reflected by high expression of co-stimulatory molecules and release of IL-12p70 and TNF-α. Furthermore, cDC1s efficiently primed alloreactive T cells, potently cross-presented long-peptides and boosted expansion of minor histocompatibility antigen-experienced T cells. Moreover, they strongly enhanced NK cell activation, degranulation and anti-leukemic reactivity. Together, we developed a robust culture protocol to generate highly functional blood DC subsets for in vivo application as tailored adjuvant immunotherapy to boost innate and adaptive anti-tumor immunity in alloSCT patients. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
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