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Research paper thumbnail of Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade

Cells, 2021

DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from ... more DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from the human DCOne myeloid leukemic cell line. This results in a vaccine comprising a broad array of endogenous tumor antigens combined with a mature dendritic cell (mDC) costimulatory profile, functioning as a local inflammatory adjuvant when injected into an allogeneic recipient. Intradermal DCP-001 vaccination has been shown to be safe and feasible as a post-remission therapy in acute myeloid leukemia. In the current study, the mode of action of DCP-001 was further characterized by static and dynamic analysis of the interaction between labelled DCP-001 and host antigen-presenting cells (APCs). Direct cell–cell interactions and uptake of DCP-001 cellular content by APCs were shown to depend on DCP-001 cell surface expression of calreticulin and phosphatidylserine, while blockade of CD47 enhanced the process. Injection of DCP-001 in an ex vivo human skin model led to its uptake by activate...

Research paper thumbnail of 171 Preclinical studies support therapeutic application of the leukemic cell-based cancer relapse vaccine DCP-001 in ovarian cancer

Journal for ImmunoTherapy of Cancer, 2020

BackgroundOvarian cancer (OC) is the gynecological malignancy with the highest mortality due to t... more BackgroundOvarian cancer (OC) is the gynecological malignancy with the highest mortality due to the late diagnosis of disease and a high rate of relapse following initial therapy. Immunotherapy in combination with standard treatment modalities has emerged as an encouraging treatment approach to surmount this unmet medical need. DCP-001 is a cancer relapse vaccine derived from the DCOne human leukemic cell line and is currently progressing through clinical trials in hematological malignancies. During manufacturing, DCOne cells are shifted towards a mature dendritic cell phenotype, rendering the cells highly immunogenic and providing the basis for DCP-001, which is administered as an intradermal vaccine. DCOne cells express multiple common tumor associated antigens (TAA) such as WT-1, RHAMM, PRAME and MUC-1, which have been documented as potential target antigens in ovarian cancer. This observation suggests that DCP-001 vaccination may also have an anti-tumor effect in OC. To support ...

Research paper thumbnail of Sequences derived from the highly antigenic VP1 region 140 to 160 of foot-and-mouth disease virus do not prime for a bovine T-cell response against intact virus

Journal of Virology, 1995

Although VP1 region 140 to 160 of foot-and-mouth disease virus (FMDV) is able to elicit neutraliz... more Although VP1 region 140 to 160 of foot-and-mouth disease virus (FMDV) is able to elicit neutralizing antibody in cattle, the protection against virus challenge that is conferred by peptide immunization is often poor. Here, we show that bovine T cells primed with peptides derived from this region generally show no reactivity to intact FMDV. In contrast, T-cell epitope VP4[20-34] is able to prime for a virus-specific response.

Research paper thumbnail of The early nodulin transcript ENOD2 is located in the nodule parenchyma (inner cortex) of pea and soybean root nodules

Research paper thumbnail of Combined Prednisolone Treatment and a High-Fat Diet in Mice Both Induce Hyperglycemia, but Alter Hepatic Glucose Metabolism Differentially

The Endocrine Society's 93rd Annual Meeting & Expo, June 4–7, 2011 - Boston, 2011

Research paper thumbnail of Proliferative lymphocyte responses to foot-and-mouth disease virus and three FMDV peptides after vaccination or immunization with these peptides in cattle

Immunology, 1992

We studied proliferative responses of bovine T lymphocytes to foot-and-mouth disease virus (FMDV)... more We studied proliferative responses of bovine T lymphocytes to foot-and-mouth disease virus (FMDV) serotypes A, O and C as well as to three peptides including the two major B-cell epitopes of FMDV (VP1[141-156] and VP1[200-213]). Peripheral blood mononuclear cells (PBMC) from cattle previously vaccinated with monovalent vaccine responded to both homotypic and heterotypic virus strains. Of 14 FMDV-specific bovine T-cell clones, which were prepared from PBMC of an animal vaccinated with the trivalent vaccine, 11 reacted to each of the three serotypes A, O and C. This indicates that several T-cell epitopes might be conserved among these serotypes. PBMC from one of two cattle immunized with VP1[141-156]KLH, one of two cattle immunized with VP1[200-213]KLH and two of three cattle immunized with CC-VP1[200-213]-PPS-VP1[141-156]-PCG responded to the homotypic virus strain. After immunizations with VP1[200-213]KLH also heterotypic responses were found. Thus, it appears that these two B-cell ...

Research paper thumbnail of Secreted melanoma inhibitory activity (MIA) is a biomarker of chondrocyte anabolism

Research paper thumbnail of Lack of a clinically relevant effect of sugammadex on anti-Xa activity or activated partial thromboplastin time following pretreatment with either unfractionated or low-molecular-weight heparin in healthy subjects

Int. Journal of Clinical Pharmacology and Therapeutics, 2014

To investigate the potential effect of sugammadex on anti-Xa anticoagulantactivity of enoxaparin ... more To investigate the potential effect of sugammadex on anti-Xa anticoagulantactivity of enoxaparin and the activated partial thromboplastin time (APTT) of unfractionated heparin (UFH). This two-part, randomized, double-blind, placebocontrolled, four-period cross-over study was performed in healthy males (18 - 45 years). In each period, subjects received 40 mg enoxaparin (in part 1), 5,000 units UFH (in part 2), or placebo followed by 4 or 16 mg/kg sugammadex, or placebo. Treatments were separated by ≥ 4 days. Primary endpoints were anti-Xa activity and APTT both time-averaged from 3 to 30 minutes post-dose. Geometric mean ratios (GMRs) and their two-sided 90% confidence limits were calculated for anticoagulant plus sugammadex (4 or 16 mg/kg) vs. anticoagulant plus placebo. The pre-specified threshold for a potential effect of clinical relevance was a 90% upper confidence limit (UCL) > 1.50. In part 1 (n = 13), the 90% UCLs were 1.07 and 1.08 for GMRs of anti-Xa activity after dosing with 4 and 16 mg/kg sugammadex, respectively. In part 2 (n = 43), the 90% UCLs for GMRs of APTT were 1.06 and 1.15. Neither sugammadex dose produced a treatment effect that met the pre-specified criterion for potential clinical relevance. Treatments were generally well tolerated. In healthy subjects, treatment with 4 mg/kg and 16 mg/kg sugammadex did not change either anti-Xa activity or APTT to a clinically meaningful extent following pretreatments with enoxaparin or UFH.

Research paper thumbnail of Org 214007-0: A Novel Non-Steroidal Selective Glucocorticoid Receptor Modulator with Full Anti-Inflammatory Properties and Improved Therapeutic Index

Research paper thumbnail of Hormonal stimulation for IVF treatment positively affects the CD56bright/CD56dim NK cell ratio of the endometrium during the window of implantation

Molecular Human Reproduction, 2004

Research paper thumbnail of Membrane-bound HLA-G activates proliferation and interferon-  production by uterine natural killer cells

Molecular Human Reproduction, 2004

Research paper thumbnail of Detection of HLA-G by a specific sandwich ELISA using monoclonal antibodies G233 and 56B

Molecular Human Reproduction, 2002

Research paper thumbnail of Soluble HLA-G promotes Th1-type cytokine production by cytokine-activated uterine and peripheral natural killer cells

MHR: Basic science of reproductive medicine, 2006

Research paper thumbnail of The proportion of follicular fluid CD16+CD56DIM NK cells is increased in IVF patients with idiopathic infertility

Journal of Reproductive Immunology, 2003

One-fifth of all in-vitro fertilization (IVF) patients suffer from idiopathic infertility. A low ... more One-fifth of all in-vitro fertilization (IVF) patients suffer from idiopathic infertility. A low fertilization rate is one of the most characteristic features of IVF in this group, probably caused by oocyte dysfunction. We speculate that an altered lymphocyte profile in follicular fluid (FF) may affect oocyte function and thus play a role in idiopathic infertility. Therefore, we compared levels of lymphocyte populations present in FF of 11 patients with idiopathic infertility (study group) with 29 patients in the control group, i.e. severe male factor infertility (n=17) or tubal factor infertility (n=12). Triple color flow cytometry was used to discriminate between T cells and NK cell subpopulations. In the idiopathic infertility group, a shift from T to NK cells was observed in FF as compared to the control group, caused mainly by a significant higher level of NK cells--20.3 and 13.6% (P<0.05), respectively. This high level of NK cells was due to a rise of the CD16+CD56dim NK cell subset. In peripheral blood, the NK cell levels showed a similar although not significant trend (P=0.08). As the CD16+CD56dim NK cell subpopulation is known for its cytotoxic properties, this subpopulation may negatively affect folliculogenesis and oocyte maturation, reflected by a diminished fertilization rate in the idiopathic infertility group. An altered lymphocyte profile in FF could therefore influence fertility in these patients.

Research paper thumbnail of CD4 rat × rat and mouse × rat T cell hybridomas produced by fusion of established T cell lines and clones to W/Fu (C58NT)D

Journal of Immunological Methods, 1991

Research paper thumbnail of T cell-stimulatory Fragments of Foot-and-mouth Disease Virus Released by Mild Treatment With Cathepsin D

Journal of General Virology, 1994

Research paper thumbnail of Levels of soluble HLA‐G in amniotic fluid are related to the sex of the offspring

European Journal of Immunogenetics, 2003

SummaryAlthough HLA‐G is thought to play a modulatory role in the immune system, its function and... more SummaryAlthough HLA‐G is thought to play a modulatory role in the immune system, its function and expression require to be elucidated. We analysed soluble HLA‐G levels in mid‐trimester amniotic fluid (n = 64) from uncomplicated pregnancies. We found a decrease in soluble HLA‐G levels for female offspring as compared to male offspring (P < 0.007). This may be a consequence of the immuno‐modulatory capacity of HLA‐G.

Research paper thumbnail of No clinically relevant interaction between sugammadex and aspirin on platelet aggregation and coagulation parameters

Int. Journal of Clinical Pharmacology and Therapeutics, 2013

Research paper thumbnail of Prednisolone-induced changes in gene-expression profiles in healthy volunteers

Pharmacogenomics, 2011

Prednisolone and other glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressive d... more Prednisolone and other glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressive drugs. However, prolonged use at a medium or high dose is hampered by side effects of which the metabolic side effects are most evident. Relatively little is known about their effect on gene-expression in vivo, the effect on cell subpopulations and the relation to the efficacy and side effects of GCs.

Research paper thumbnail of Production and characterisation of an antiserum raised against recombinant rainbow trout (Oncorhynchus mykiss) MHC class II beta-chain (MhcOnmy-DAB)

Fish & Shellfish Immunology, 1998

Research paper thumbnail of Transfer of Cellular Content from the Allogeneic Cell-Based Cancer Vaccine DCP-001 to Host Dendritic Cells Hinges on Phosphatidylserine and Is Enhanced by CD47 Blockade

Cells, 2021

DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from ... more DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from the human DCOne myeloid leukemic cell line. This results in a vaccine comprising a broad array of endogenous tumor antigens combined with a mature dendritic cell (mDC) costimulatory profile, functioning as a local inflammatory adjuvant when injected into an allogeneic recipient. Intradermal DCP-001 vaccination has been shown to be safe and feasible as a post-remission therapy in acute myeloid leukemia. In the current study, the mode of action of DCP-001 was further characterized by static and dynamic analysis of the interaction between labelled DCP-001 and host antigen-presenting cells (APCs). Direct cell–cell interactions and uptake of DCP-001 cellular content by APCs were shown to depend on DCP-001 cell surface expression of calreticulin and phosphatidylserine, while blockade of CD47 enhanced the process. Injection of DCP-001 in an ex vivo human skin model led to its uptake by activate...

Research paper thumbnail of 171 Preclinical studies support therapeutic application of the leukemic cell-based cancer relapse vaccine DCP-001 in ovarian cancer

Journal for ImmunoTherapy of Cancer, 2020

BackgroundOvarian cancer (OC) is the gynecological malignancy with the highest mortality due to t... more BackgroundOvarian cancer (OC) is the gynecological malignancy with the highest mortality due to the late diagnosis of disease and a high rate of relapse following initial therapy. Immunotherapy in combination with standard treatment modalities has emerged as an encouraging treatment approach to surmount this unmet medical need. DCP-001 is a cancer relapse vaccine derived from the DCOne human leukemic cell line and is currently progressing through clinical trials in hematological malignancies. During manufacturing, DCOne cells are shifted towards a mature dendritic cell phenotype, rendering the cells highly immunogenic and providing the basis for DCP-001, which is administered as an intradermal vaccine. DCOne cells express multiple common tumor associated antigens (TAA) such as WT-1, RHAMM, PRAME and MUC-1, which have been documented as potential target antigens in ovarian cancer. This observation suggests that DCP-001 vaccination may also have an anti-tumor effect in OC. To support ...

Research paper thumbnail of Sequences derived from the highly antigenic VP1 region 140 to 160 of foot-and-mouth disease virus do not prime for a bovine T-cell response against intact virus

Journal of Virology, 1995

Although VP1 region 140 to 160 of foot-and-mouth disease virus (FMDV) is able to elicit neutraliz... more Although VP1 region 140 to 160 of foot-and-mouth disease virus (FMDV) is able to elicit neutralizing antibody in cattle, the protection against virus challenge that is conferred by peptide immunization is often poor. Here, we show that bovine T cells primed with peptides derived from this region generally show no reactivity to intact FMDV. In contrast, T-cell epitope VP4[20-34] is able to prime for a virus-specific response.

Research paper thumbnail of The early nodulin transcript ENOD2 is located in the nodule parenchyma (inner cortex) of pea and soybean root nodules

Research paper thumbnail of Combined Prednisolone Treatment and a High-Fat Diet in Mice Both Induce Hyperglycemia, but Alter Hepatic Glucose Metabolism Differentially

The Endocrine Society's 93rd Annual Meeting & Expo, June 4–7, 2011 - Boston, 2011

Research paper thumbnail of Proliferative lymphocyte responses to foot-and-mouth disease virus and three FMDV peptides after vaccination or immunization with these peptides in cattle

Immunology, 1992

We studied proliferative responses of bovine T lymphocytes to foot-and-mouth disease virus (FMDV)... more We studied proliferative responses of bovine T lymphocytes to foot-and-mouth disease virus (FMDV) serotypes A, O and C as well as to three peptides including the two major B-cell epitopes of FMDV (VP1[141-156] and VP1[200-213]). Peripheral blood mononuclear cells (PBMC) from cattle previously vaccinated with monovalent vaccine responded to both homotypic and heterotypic virus strains. Of 14 FMDV-specific bovine T-cell clones, which were prepared from PBMC of an animal vaccinated with the trivalent vaccine, 11 reacted to each of the three serotypes A, O and C. This indicates that several T-cell epitopes might be conserved among these serotypes. PBMC from one of two cattle immunized with VP1[141-156]KLH, one of two cattle immunized with VP1[200-213]KLH and two of three cattle immunized with CC-VP1[200-213]-PPS-VP1[141-156]-PCG responded to the homotypic virus strain. After immunizations with VP1[200-213]KLH also heterotypic responses were found. Thus, it appears that these two B-cell ...

Research paper thumbnail of Secreted melanoma inhibitory activity (MIA) is a biomarker of chondrocyte anabolism

Research paper thumbnail of Lack of a clinically relevant effect of sugammadex on anti-Xa activity or activated partial thromboplastin time following pretreatment with either unfractionated or low-molecular-weight heparin in healthy subjects

Int. Journal of Clinical Pharmacology and Therapeutics, 2014

To investigate the potential effect of sugammadex on anti-Xa anticoagulantactivity of enoxaparin ... more To investigate the potential effect of sugammadex on anti-Xa anticoagulantactivity of enoxaparin and the activated partial thromboplastin time (APTT) of unfractionated heparin (UFH). This two-part, randomized, double-blind, placebocontrolled, four-period cross-over study was performed in healthy males (18 - 45 years). In each period, subjects received 40 mg enoxaparin (in part 1), 5,000 units UFH (in part 2), or placebo followed by 4 or 16 mg/kg sugammadex, or placebo. Treatments were separated by ≥ 4 days. Primary endpoints were anti-Xa activity and APTT both time-averaged from 3 to 30 minutes post-dose. Geometric mean ratios (GMRs) and their two-sided 90% confidence limits were calculated for anticoagulant plus sugammadex (4 or 16 mg/kg) vs. anticoagulant plus placebo. The pre-specified threshold for a potential effect of clinical relevance was a 90% upper confidence limit (UCL) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 1.50. In part 1 (n = 13), the 90% UCLs were 1.07 and 1.08 for GMRs of anti-Xa activity after dosing with 4 and 16 mg/kg sugammadex, respectively. In part 2 (n = 43), the 90% UCLs for GMRs of APTT were 1.06 and 1.15. Neither sugammadex dose produced a treatment effect that met the pre-specified criterion for potential clinical relevance. Treatments were generally well tolerated. In healthy subjects, treatment with 4 mg/kg and 16 mg/kg sugammadex did not change either anti-Xa activity or APTT to a clinically meaningful extent following pretreatments with enoxaparin or UFH.

Research paper thumbnail of Org 214007-0: A Novel Non-Steroidal Selective Glucocorticoid Receptor Modulator with Full Anti-Inflammatory Properties and Improved Therapeutic Index

Research paper thumbnail of Hormonal stimulation for IVF treatment positively affects the CD56bright/CD56dim NK cell ratio of the endometrium during the window of implantation

Molecular Human Reproduction, 2004

Research paper thumbnail of Membrane-bound HLA-G activates proliferation and interferon-  production by uterine natural killer cells

Molecular Human Reproduction, 2004

Research paper thumbnail of Detection of HLA-G by a specific sandwich ELISA using monoclonal antibodies G233 and 56B

Molecular Human Reproduction, 2002

Research paper thumbnail of Soluble HLA-G promotes Th1-type cytokine production by cytokine-activated uterine and peripheral natural killer cells

MHR: Basic science of reproductive medicine, 2006

Research paper thumbnail of The proportion of follicular fluid CD16+CD56DIM NK cells is increased in IVF patients with idiopathic infertility

Journal of Reproductive Immunology, 2003

One-fifth of all in-vitro fertilization (IVF) patients suffer from idiopathic infertility. A low ... more One-fifth of all in-vitro fertilization (IVF) patients suffer from idiopathic infertility. A low fertilization rate is one of the most characteristic features of IVF in this group, probably caused by oocyte dysfunction. We speculate that an altered lymphocyte profile in follicular fluid (FF) may affect oocyte function and thus play a role in idiopathic infertility. Therefore, we compared levels of lymphocyte populations present in FF of 11 patients with idiopathic infertility (study group) with 29 patients in the control group, i.e. severe male factor infertility (n=17) or tubal factor infertility (n=12). Triple color flow cytometry was used to discriminate between T cells and NK cell subpopulations. In the idiopathic infertility group, a shift from T to NK cells was observed in FF as compared to the control group, caused mainly by a significant higher level of NK cells--20.3 and 13.6% (P&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05), respectively. This high level of NK cells was due to a rise of the CD16+CD56dim NK cell subset. In peripheral blood, the NK cell levels showed a similar although not significant trend (P=0.08). As the CD16+CD56dim NK cell subpopulation is known for its cytotoxic properties, this subpopulation may negatively affect folliculogenesis and oocyte maturation, reflected by a diminished fertilization rate in the idiopathic infertility group. An altered lymphocyte profile in FF could therefore influence fertility in these patients.

Research paper thumbnail of CD4 rat × rat and mouse × rat T cell hybridomas produced by fusion of established T cell lines and clones to W/Fu (C58NT)D

Journal of Immunological Methods, 1991

Research paper thumbnail of T cell-stimulatory Fragments of Foot-and-mouth Disease Virus Released by Mild Treatment With Cathepsin D

Journal of General Virology, 1994

Research paper thumbnail of Levels of soluble HLA‐G in amniotic fluid are related to the sex of the offspring

European Journal of Immunogenetics, 2003

SummaryAlthough HLA‐G is thought to play a modulatory role in the immune system, its function and... more SummaryAlthough HLA‐G is thought to play a modulatory role in the immune system, its function and expression require to be elucidated. We analysed soluble HLA‐G levels in mid‐trimester amniotic fluid (n = 64) from uncomplicated pregnancies. We found a decrease in soluble HLA‐G levels for female offspring as compared to male offspring (P < 0.007). This may be a consequence of the immuno‐modulatory capacity of HLA‐G.

Research paper thumbnail of No clinically relevant interaction between sugammadex and aspirin on platelet aggregation and coagulation parameters

Int. Journal of Clinical Pharmacology and Therapeutics, 2013

Research paper thumbnail of Prednisolone-induced changes in gene-expression profiles in healthy volunteers

Pharmacogenomics, 2011

Prednisolone and other glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressive d... more Prednisolone and other glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressive drugs. However, prolonged use at a medium or high dose is hampered by side effects of which the metabolic side effects are most evident. Relatively little is known about their effect on gene-expression in vivo, the effect on cell subpopulations and the relation to the efficacy and side effects of GCs.

Research paper thumbnail of Production and characterisation of an antiserum raised against recombinant rainbow trout (Oncorhynchus mykiss) MHC class II beta-chain (MhcOnmy-DAB)

Fish & Shellfish Immunology, 1998