A5044835836- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Biosimilars and Bioanalytical Methods
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Single-cell and spatial transcriptomics
- Cytomegalovirus and herpesvirus research
- Nanowire Synthesis and Applications
- Cancer Immunotherapy and Biomarkers
- Viral Infectious Diseases and Gene Expression in Insects
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Bioeconomy and Sustainability Development
- vaccines and immunoinformatics approaches
- Cancer Research and Treatments
- Herpesvirus Infections and Treatments
- Parvovirus B19 Infection Studies
Ghent University
2018-2024
Cancer Research Institute Ghent
2021-2024
Ghent University Hospital
2018-2024
Recent clinical trials have shown that adoptive chimeric antigen receptor (CAR) T cell therapy is a very potent and possibly curative option in the treatment of B leukemias lymphomas. However, targeting single may not be sufficient, relapse due to emergence negative leukemic cells occur. A potential strategy counter outgrowth escape variants broaden specificity CAR by incorporation multiple recognition domains tandem. As proof concept, we here describe bispecific which chain variable...
Non-small cell lung cancer (NSCLC) is known for high relapse rates despite resection in early stages. Here, we present the results of a phase I clinical trial which dendritic (DC) vaccine targeting patient-individual neoantigens evaluated patients with resected NSCLC. Vaccine manufacturing feasible six 10 enrolled patients. Toxicity limited to grade 1-2 adverse events. Systemic T responses are observed five out vaccinated patients, remaining detectable up 19 months post vaccination....
CD70 is an attractive target for chimeric antigen receptor (CAR) T-cell therapy the treatment of both solid and liquid malignancies. However, functionality CD70-specific CAR T cells modest. We optimized a VHH-based (nanoCAR). evaluated nanoCARs in clinically relevant models vitro, using co-cultures nanoCAR with malignant rhabdoid tumor organoids, vivo, diffuse large B-cell lymphoma patient-derived xenograft (PDX) model. Although were highly efficient organoid co-cultures, they showed only...
Recent approval of chimeric antigen receptor (CAR) T cell therapy by the European Medicines Agency (EMA)/Federal and Drug Administration (FDA) remarkable results CAR clinical trials illustrate curative potential this therapy. While CARs against a multitude different antigens are being developed tested (pre)clinically, there is still need for optimization. The use single-chain variable fragments (scFvs) as targeting moieties hampers quick generation functional could potentially limit...
In the human thymus, a CD10+ PD-1+ TCRαβ+ differentiation pathway diverges from conventional single positive T cell lineages at early double-positive stage. Here, we identify progeny of this unconventional lineage in antigen-inexperienced blood. These cells (UTCs) thymus and blood share transcriptomic profile, characterized by hallmark transcription factors (i.e., ZNF683 IKZF2), polyclonal TCR repertoire with autoreactive features, exhibiting bias toward TCRα chain rearrangements....
Messenger RNA (mRNA) has become a promising tool in therapeutic cancer vaccine strategies. Owing to its flexible design and rapid production, mRNA is an attractive antigen delivery format for vaccines targeting mutated peptides expressed tumor-the so-called neoantigens. These neoantigens are rarely shared between patients, inclusion of these antigens requires the production individual batches patient-tailored mRNA. The authors have developed MIDRIXNEO, personalized mRNA-loaded dendritic cell...
Chimeric antigen receptor (CAR) T-cells have shown great promise in the treatment of B-cell malignancies. For acute myeloid leukemia (AML), however, optimal target surface has yet to be discovered. Alternatively, T-cell (TCR)-redirected intracellular antigens, marking a broader territory available antigens. Currently, adoptive TCR therapy uses peripheral blood lymphocytes for introduction transgenic TCR. However, this can cause graft-versus-host disease, due mispairing introduced and...
The Wiskott-Aldrich syndrome (WAS) is an X-linked primary immune deficiency caused by a mutation in the WAS gene. This leads to altered or absent protein (WASp) expression and function resulting thrombocytopenia, eczema, recurrent infections, autoimmunity. In T cells, WASp required for synapse formation. Patients with show reduced numbers of peripheral blood lymphocytes T-cell receptor repertoire.
Human thymic CD8αα+ CD10+ PD-1+ αβ T cells selected through early agonist selection have been proposed as the putative precursors of human intestinal intraepithelial lymphocytes (IELs). However, progeny these precursor in blood or tissues has not yet characterized. Here, we studied phenotypical and transcriptional differentiation IEL (IELp) lineage upon vitro exposure to cytokines prominent peripheral such interleukin-15 (IL-15) inflammatory interleukin-12 (IL-12) interleukin-18 (IL-18). We...
T cell receptor (TCR)-redirected cells target intracellular antigens such as Wilms' tumor 1 (WT1), a tumor-associated antigen overexpressed in several malignancies, including acute myeloid leukemia (AML). For both chimeric (CAR)- and TCR-redirected cells, clinical studies indicate that subsets with less-differentiated phenotype (e.g. stem memory TSCM) survive longer mediate superior anti-tumor effects vivo opposed to more terminally differentiated cells. Cytokines added during vitro ex...
Abstract In the human thymus, a CD10 + PD-1 TCRαβ differentiation pathway diverges from conventional single positive T cell lineages at early double stage. These cells are phenotypically and functionally similar to murine unconventional intraepithelial lymphocyte (uIEL) precursors. Here, progeny of uIEL lineage was identified in antigen-inexperienced blood. The uIELs thymus peripheral blood share transcriptomic profile, characterized by hallmark transcription factors (i.e. ZNF683 IKZF2 ),...
Abstract CD70 is an attractive target for chimeric antigen receptor (CAR) T cell therapy as treatment both solid and liquid malignancies. However, functionality of CD70-specific CARs only modest. Here, we optimized a VHH based CAR (nanoCAR). We evaluated the nanoCARs in clinically relevant models vitro , using co-cultures nanoCAR cells with malignant rhabdoid tumor organoids, vivo by diffuse large B lymphoma (DLBCL) patient-derived xenograft (PDX) model. Whereas were highly efficient...
<p>CD70-specific nanoCAR T-cells incubated with CD70+ JD033T organoid line</p>
<p>CD70-specific nanoCAR T-cells incorporating 4-1BB as costimulatory domain show the highest efficacy</p>
<div>Abstract<p>CD70 is an attractive target for chimeric antigen receptor (CAR) T-cell therapy the treatment of both solid and liquid malignancies. However, functionality CD70-specific CAR T cells modest. We optimized a VHH-based (nanoCAR). evaluated nanoCARs in clinically relevant models <i>in vitro</i>, using co-cultures nanoCAR with malignant rhabdoid tumor organoids, vivo</i>, diffuse large B-cell lymphoma patient-derived xenograft (PDX) model. Although...
<p>CD20-specific nanoCAR T-cells incubated with CD70+ JD033T organoid line</p>
<p>CD70 expression on nanoCAR T-cells.</p>
<div>Abstract<p>CD70 is an attractive target for chimeric antigen receptor (CAR) T-cell therapy the treatment of both solid and liquid malignancies. However, functionality CD70-specific CAR T cells modest. We optimized a VHH-based (nanoCAR). evaluated nanoCARs in clinically relevant models <i>in vitro</i>, using co-cultures nanoCAR with malignant rhabdoid tumor organoids, vivo</i>, diffuse large B-cell lymphoma patient-derived xenograft (PDX) model. Although...
<p>Single cell analysis of nanoCAR T-cell treated mice result in 12 defined clusters.</p>
<p>Differentially expressed genes in bulk RNAseq data from CD70-4_1BB:ζ KO vs WT</p>
<p>Differentially expressed genes in nanoCAR T-cells from cluster CD8WT vs CD4WT</p>