Molecular mechanism and inhibition of extracellular vesicle mediated PD L1 relea...
Molecular mechanism and inhibition of extracellular vesicle mediated PD L1 release in melanoma cells
Harnessing the power of the immune system to treat cancer has long been a sought after goal of oncological research. Immune checkpoint inhibitors, such as anti-programmed death receptor 1 (PD-1) blockade therapies, have now taken...
ver más
¿Tienes un proyecto y buscas un partner? Gracias a nuestro motor inteligente podemos recomendarte los mejores socios y ponerte en contacto con ellos. Te lo explicamos en este video
Proyectos interesantes
TESTIMONY
Tumor Endothelial Cells Gatekeepers Of Anti Tumor Immunity
178K€
Cerrado
EVasion
Evasion of antitumor immunity and immunotherapy by melanoma...
173K€
Cerrado
IMMUNO-TEX
Overcoming resistance to immunotherapy: Immunostimulatory tu...
2M€
Cerrado
SAF2015-65157-R
COMBINACION DE TERAPIA CELULAR ADOPTIVA Y EXPRESION INTRATUM...
Cerrado
EUIN2017-87851
INTEGRACION DE OMICAS PARA LA TERAPIA DIRIGIDA EN INMUNOTERA...
10K€
Cerrado
SAF2017-83732-R
REPROGRAMACION DEL MICROAMBIENTE TUMORAL PARA AUMENTAR LA EF...
339K€
Cerrado
Información proyecto UNPACK PD-L1
Duración del proyecto: 33 meses
Fecha Inicio: 2019-04-09
Fecha Fin: 2022-01-31
Líder del proyecto
STICHTING AMSTERDAM UMC
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Presupuesto del proyecto
176K€
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
Harnessing the power of the immune system to treat cancer has long been a sought after goal of oncological research. Immune checkpoint inhibitors, such as anti-programmed death receptor 1 (PD-1) blockade therapies, have now taken center stage. However not all patients respond, highlighting gaps in our understanding of the mechanisms of tumour immunosuppression. Upregulation of the PD-1 ligand (PD-L1) on tumour cells initiated this therapeutic direction, yet it is becoming clear that the modality of PD-L1-mediated immune suppression is not limited to the plasma membrane. Like many tumor cells, melanoma cells secrete small extracellular vesicles (EVs) with pro-tumorigenic properties. Melanoma EVs express PD-L1 that suppress T cell function and facilitate tumour growth in pre-clinical mouse models. This systemic mechanism is clinically relevant, as circulating EV-PD-L1 levels can stratify anti-PD-1 clinical responders from non-responders. Thus inhibiting EV-PD-L1 may increase anti-PD-1 efficacy and broaden the responder bracket. One plausible strategy would be to block tumor EV secretion, yet little is known about the molecular mechanisms that drive PD-L1 loading and release. Herein, I intend to uncover the molecular mechanisms of EV PD-L1 release from melanoma cells using state-of-the-art optical and bioluminescent reporters to reveal novel druggable targets. This basic knowledge will be exploited to guide subsequent inhibition, through a drug screen for candidates that inhibit EV-PD-L1 release and restore T cell function. Ideally the outcome of this in vitro study will provide a strong rationale for combining anti-PD-1 agents with inhibitors of EV-PD-L1 secretion, to be tested in pre-clinical mouse models. If successful, melanoma EV blockade may remove the unanticipated bottlenecks that surround the efficacy of anti-PD-1 therapy. In the long term this study is meant to lay groundwork for tumor EV inhibition as a therapeutic strategy for cancer types beyond melanoma.