A5057007080- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Viral Infectious Diseases and Gene Expression in Insects
- CRISPR and Genetic Engineering
- Synthesis and Biological Evaluation
- Chronic Lymphocytic Leukemia Research
- Pancreatic and Hepatic Oncology Research
- Immune cells in cancer
- Ubiquitin and proteasome pathways
- Protein Degradation and Inhibitors
- Advancements in Semiconductor Devices and Circuit Design
Oncode Institute
2019-2024
The Netherlands Cancer Institute
2019-2024
MorphoSys (Germany)
2023
Abstract Although immune checkpoint blockade (ICB) has shown remarkable clinical benefit in a subset of patients with melanoma and lung cancer, most experience no durable benefit. The receptor tyrosine kinase AXL is commonly implicated therapy resistance may serve as marker for therapy-refractory tumors, example melanoma, we previously demonstrated. Here, show that enapotamab vedotin (EnaV), an antibody–drug conjugate targeting AXL, effectively targets tumors display insensitivity to...
The cytokine IFNγ differentially impacts on tumors upon immune checkpoint blockade (ICB). Despite our understanding of downstream signaling events, less is known about regulation its receptor (IFNγ-R1). With an unbiased genome-wide CRISPR/Cas9 screen for critical regulators IFNγ-R1 cell surface abundance, we identify STUB1 as E3 ubiquitin ligase in complex with signal-relaying kinase JAK1. mediates ubiquitination-dependent proteasomal degradation IFNγ-R1/JAK1 through
Tumor escape mechanisms for immunotherapy include deficiencies in antigen presentation, diminishing adaptive CD8+ T cell antitumor activity. Although innate natural killer (NK) cells are triggered by loss of MHC class I, their response is often inadequate. To increase tumor susceptibility to both and immune elimination, we performed parallel genome-wide CRISPR-Cas9 knockout screens under NK pressure. We identify all components, RNF31, RBCK1, SHARPIN, the linear ubiquitination chain assembly...
Genes limiting T cell antitumor activity may serve as therapeutic targets. It has not been systematically studied whether there are regulators that uniquely or broadly contribute to fitness. We perform genome-scale CRISPR-Cas9 knockout screens in primary CD8 cells uncover genes negatively impacting fitness upon three modes of stimulation: (1) intense, triggering activation-induced death (AICD); (2) acute, expansion; (3) chronic, causing dysfunction. Besides established regulators, we...
Adoptive transfer of genetically modified or donor-derived T cells can efficiently eradicate human tumors but is also frequently associated with major toxicity. There are several switches that be used to kill the infused cell pool in case toxicity, irreversible nature these suicide means therapeutic effect lost when they used. To address this issue, we engineered a small-molecule responsive genetic safety switch absence drug robustly blocked cytotoxicity and cytokine expression primary...
Blockade of the programmed cell death protein 1 (PD-1) immune checkpoint (ICB) is revolutionizing cancer therapy, but little known about mechanisms governing its expression on CD8 T cells. Because PD-1 induced during activation cells, we set out to uncover regulators whose inhibition suppresses abundance without adversely impacting activation.
Abstract Despite the success of immune checkpoint blockade (ICB) most patients fail to respond durably, in part owing reduced interferon gamma (IFNγ) sensitivity. Thus, elevating tumor IFNγ-receptor 1 (IFNγ-R1) expression enhance IFNγ-mediated cytotoxicity is potential clinical interest. Here, we show that increased IFNγ-R1 sensitizes tumors killing. To unveil largely undefined mechanism governing expression, performed a genome-wide CRISPR/Cas9 screen for suppressors its cell surface...
<div>Abstract<p>Although immune checkpoint blockade (ICB) has shown remarkable clinical benefit in a subset of patients with melanoma and lung cancer, most experience no durable benefit. The receptor tyrosine kinase AXL is commonly implicated therapy resistance may serve as marker for therapy-refractory tumors, example melanoma, we previously demonstrated. Here, show that enapotamab vedotin (EnaV), an antibody–drug conjugate targeting AXL, effectively targets tumors display...
<p>Supplementary figures 1-5 and legends</p>
<p>Supplementary Table 2 Differentially expressed proteins, comparing EnaV-treated tumors to control tumors</p>
<p>Supplementary Table 1 Differentially expressed genes of PCA3, comparing EnaV-treated tumors to control tumors</p>
<p>Supplementary Table 1 Differentially expressed genes of PCA3, comparing EnaV-treated tumors to control tumors</p>
<p>Supplementary Table 2 Differentially expressed proteins, comparing EnaV-treated tumors to control tumors</p>
<p>Supplementary figures 1-5 and legends</p>
<div>Abstract<p>Adoptive transfer of genetically modified or donor-derived T cells can efficiently eradicate human tumors but is also frequently associated with major toxicity. There are several switches that be used to kill the infused cell pool in case toxicity, irreversible nature these suicide means therapeutic effect lost when they used. To address this issue, we engineered a small-molecule responsive genetic safety switch absence drug robustly blocked cytotoxicity and...
<p>Supplementary Figure S1-S8</p>
<p>Supplementary Figure S1-S8</p>
<div>Abstract<p>Adoptive transfer of genetically modified or donor-derived T cells can efficiently eradicate human tumors but is also frequently associated with major toxicity. There are several switches that be used to kill the infused cell pool in case toxicity, irreversible nature these suicide means therapeutic effect lost when they used. To address this issue, we engineered a small-molecule responsive genetic safety switch absence drug robustly blocked cytotoxicity and...
<div>Abstract<p>Although immune checkpoint blockade (ICB) has shown remarkable clinical benefit in a subset of patients with melanoma and lung cancer, most experience no durable benefit. The receptor tyrosine kinase AXL is commonly implicated therapy resistance may serve as marker for therapy-refractory tumors, example melanoma, we previously demonstrated. Here, show that enapotamab vedotin (EnaV), an antibody–drug conjugate targeting AXL, effectively targets tumors display...