A5059973952- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Biomedical Ethics and Regulation
- Virus-based gene therapy research
- Immunotherapy and Immune Responses
- Viral-associated cancers and disorders
- Health Systems, Economic Evaluations, Quality of Life
- T-cell and B-cell Immunology
- Cancer Immunotherapy and Biomarkers
- Parasite Biology and Host Interactions
- Lymphoma Diagnosis and Treatment
- Parasites and Host Interactions
- Biosimilars and Bioanalytical Methods
- Pluripotent Stem Cells Research
- Malaria Research and Control
- Pharmaceutical studies and practices
- 3D Printing in Biomedical Research
- Hematopoietic Stem Cell Transplantation
- Viral Infectious Diseases and Gene Expression in Insects
- Helminth infection and control
- Herpesvirus Infections and Treatments
- Biomedical and Engineering Education
- Pharmaceutical Economics and Policy
- Mosquito-borne diseases and control
Leiden University Medical Center
2015-2025
Hospital Universitario Puerta de Hierro Majadahonda
2018
Leiden University
2017
Erasmus MC
2003-2008
Erasmus University Rotterdam
2003-2008
Sanquin
2003
Memorial Sloan Kettering Cancer Center
2003
University of Birmingham
2003
University of Liverpool
2003
Amsterdam UMC Location Vrije Universiteit Amsterdam
2002
Abstract Malaria vaccines consisting of metabolically active Plasmodium falciparum ( Pf ) sporozoites can offer improved protection compared with currently deployed subunit vaccines. In a previous study, we demonstrated the superior protective efficacy three-dose regimen late-arresting genetically attenuated parasites administered by mosquito bite (GA2-MB) early-arresting counterparts (GA1-MB) against homologous controlled human malaria infection. Encouraged these results, explored potency...
ABSTRACT Human CD4 + T-helper 1 cell responses to Epstein-Barr virus (EBV) infection are likely be important in the maintenance of virus-specific CD8 memory and/or as antiviral effectors their own right. The present work has used overlapping peptides stimulators gamma interferon release (i) identify epitopes within four EBV latent-cycle proteins, i.e., nuclear antigens EBNA1 and EBNA3C latent membrane proteins LMP1 LMP2, (ii) determine frequency magnitude these healthy carriers. Responses...
Background aimsFew human induced pluripotent stem cell (hiPSC) lines are Good Manufacturing Practice (GMP)-compliant, limiting the clinical use of hiPSC-derived products. Here, we addressed this by establishing and validating an in-house platform to produce GMP-compliant hiPSCs that would be appropriate for producing both allogeneic autologous products.MethodsOur standard research protocol production was adapted translated into a platform. In addition generation hiPSC, entails methodology...
In neoplastic cells of EBV-positive lymphoid malignancies latent membrane protein (LMP1) is expressed. Because no adequate cellular immune response can be detected against LMP1, we investigated whether LMP1 had a direct effect on T lymphocyte activation. this study show that nanogram amounts purified recombinant (rLMP1) strongly suppresses activation cells. By sequence alignment two sequences (LALLFWL and LLLLAL) in the first transmembrane domain were identified showing strong homology to...
The genetically attenuated malaria vaccine PfSPZ-GA1 is safe, immunogenic, and has suboptimal protective efficacy in people.
Recombinase-activating gene-1 (RAG1)-deficient severe combined immunodeficiency (SCID) patients lack B and T lymphocytes due to the inability rearrange immunoglobulin cell receptor genes. Gene therapy is an alternative for those RAG1-SCID who a suitable bone marrow donor. We designed lentiviral vectors with different internal promoters driving codon-optimized RAG1 ensure optimal expression. used Rag1−/− mice as preclinical model assess efficacy of various vectors. observed that...
Abstract Epstein‐Barr virus (EBV) is associated with several human malignancies that each show different viral gene expression profiles. In such as Hodgkin's disease and nasopharyngeal carcinoma only nuclear antigen 1 (EBNA1) varying levels of latent membrane proteins 2 (LMP1 ‐2) are expressed. Since endogenously expressed EBNA1 protected from CTL recognition, LMP1 LMP2 the most likely target antigens for anti‐tumor immunotherapy. Therefore, we sought to identify in a systematic way CD8 +...
Recent technical and clinical advances with cell-based therapies (CBTs) hold great promise in the treatment of patients rare diseases those high unmet medical need. Currently majority CBTs are developed manufactured specialized academic facilities. Due to small scale, unique characteristics specific supply chain, CBT manufacturing is considered costly compared more conventional medicinal products. As a result, biomedical researchers clinicians increasingly faced cost considerations...
Background Human adenovirus can cause morbidity and mortality in immunocompromised patients after allogeneic stem cell transplantation. Reconstitution of adenovirus-specific CD4+ T cells has been reported to be associated with sustained protection from disease, but epitope specificity these responses not characterized. Since mainly no CD8+ specific for have detected transplantation, the relative contribution disease remains elucidated.Design Methods The presence human hexon-specific was...
Since HA-1-specific T cells have been shown to make a significant contribution the clinical responses in patients with relapsed leukemia, we investigated feasibility of adoptive transfer vitro induced CD8 positive leukemia after allogeneic stem cell transplantation. The generation grade T-cell lines from HA-1 negative donors was seen be feasible and 3 were treated lines. No toxicity infusion observed. Although one patient, during period stable disease, could detected peripheral blood bone...
To treat patients with refractory cytomegalovirus (CMV) reactivation after allogeneic stem cell transplantation, a phase I/II clinical study on adoptive transfer of in vitro-generated donor-derived or patient-derived CMV pp65-specific CD8+ T-cell lines was performed. Peripheral blood mononuclear cells from seropositive donors were stimulated HLA-A*0201-restricted and/or HLA-B*0702-restricted pp65 peptides (NLV/TPR) and 1 day stimulation interferon-γ)-producing enriched using the CliniMACS...
In the last decade, many clinical trials with gene- and cell-based therapies were performed increasing interest in development was established by (national) authorities, academic developers, commercial companies. However, until now only eight products have received marketing authorization (MA) approval. this study, a comprehensive overview of Europe is presented, strong focus on product-technical aspects. Public data regarding therapies, obtained from European Union (EU) trial database...
Opportunistic viral infections can cause serious morbidity and mortality in immunocompromised patients after allogeneic stem cell transplantation. Clinical studies have shown that adoptive transfer of donor-derived T cells specific for cytomegalovirus (CMV), Epstein-Barr virus (EBV), or human adenovirus (HAdV) be a safe effective treatment with these major pathogens. The aim this study was to develop method the simultaneous isolation coordinated CD8+ CD4+ memory T-cell responses against...
A sequential, two-step procedure in which T-cell-depleted allogeneic stem cell transplantation is followed by treatment with donor lymphocyte infusion at 6 months can significantly reduce the risk and severity of graft-versus-host disease, postponed induction beneficial graft-versus-leukemia effect. However, patients high-risk leukemia have a substantial relapse early after transplantation, time when administration lymphocytes has high likelihood resulting disturbing favorable balance...
Graft-versus-leukemia (GVL) reactivity after HLA-matched allogeneic stem cell transplantation (alloSCT) is mainly mediated by donor T cells recognizing minor histocompatibility antigens (MiHA). If MiHA are targeted that exclusively expressed on hematopoietic of recipient origin, selective GVL without severe graft-versus-host-disease (GVHD) may occur. In this phase I study we explored HA-1H-TCR gene transfer into harvested from the HA-1H negative stem-cell to treat positive HLA-A*02:01...
A controlled human infection model for schistosomiasis (CHI-S) can speed up vaccine development and provides insight into early immune responses following schistosome exposure. Recently, we established CHI-S using single-sex male-only Schistosoma mansoni (Sm) cercariae in Schistosoma-naïve individuals. Given important differences antigenic profile to schistosomes of different sex, pioneered a female-only future use development.We exposed 13 healthy, adult participants 10 (n = 3) or 20 10)...
Background The presence of T cells and suppressive myeloid in epithelial ovarian cancer (EOC) correlate with good bad clinical outcome, respectively. This suggests that EOC may be sensitive to adoptive cell therapy autologous tumor-infiltrating lymphocytes (TIL), provided immunosuppression by myeloid-derived suppressor M2 macrophages is reduced. Platinum-based chemotherapy can alleviate such immunosuppression, potentially creating a window opportunity for cell-based immunotherapy. Methods We...
Progressive myopathy and exercise intolerance significantly impair quality of life in over 50% m.3243A>G mutation carriers, with no curative therapy currently available. We hypothesize that intra-arterial administration autologous, mtDNA free myogenic stem cells, mesoangioblasts, can reduce load, enhance oxidative phosphorylation, improve muscle function. To test this, the tibialis anterior muscles three carriers were damaged by eccentric before infusion 50 million/kg autologous...
Abstract Purpose: Melanoma patients progressing despite immune checkpoint blockade (ICB) may benefit from adoptive transfer of tumor infiltrating lymphocytes (TIL). Patients and Methods: We investigated the impact a pegylated interferon-alpha (IFNa) conditioning support regimen on safety efficacy TIL plus Nivolumab (NCT03638375). ICB-resistant stage III/IV melanoma were treated with without (n=9) or (n=25) IFNa. Results: The treatment was safe, side effects include IFNa-induced lymphopenia...