A5029473322- Phagocytosis and Immune Regulation
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- Cancer Research and Treatments
- Nanoparticle-Based Drug Delivery
- Galectins and Cancer Biology
- RNA Interference and Gene Delivery
- Bacteriophages and microbial interactions
- Virus-based gene therapy research
- Immune cells in cancer
- CAR-T cell therapy research
- Nanoplatforms for cancer theranostics
- Transgenic Plants and Applications
- Erythrocyte Function and Pathophysiology
- Nanoparticles: synthesis and applications
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and biological activity
- HER2/EGFR in Cancer Research
- Laser-Ablation Synthesis of Nanoparticles
- Click Chemistry and Applications
- Immune Cell Function and Interaction
- Neuroblastoma Research and Treatments
- Lymphoma Diagnosis and Treatment
- Cell Adhesion Molecules Research
Light Chain Bioscience (Switzerland)
2015-2024
Centre National de la Recherche Scientifique
2013-2015
Université Joseph Fourier
2012-2015
Centre Hospitalier Universitaire de Grenoble
2015
Translational Innovation in Medicine and Complexity
2013-2014
Université Grenoble Alpes
2013
CD47, an ubiquitously expressed innate immune checkpoint receptor that serves as a universal "don't eat me" signal of phagocytosis, is often upregulated by hematologic and solid cancers to evade surveillance. Development CD47-targeted modalities hindered the ubiquitous expression target, leading rapid drug elimination hemotoxicity including anemia. To overcome such liabilities, we have developed fully human bispecific antibody, NI-1701, designed coengage CD47 CD19 selectively on B cells....
Cancer cells develop resistance to chemotherapy, and the side effects encountered seriously limit effectiveness of treatments. For these reasons, search for alternative therapies that target cancer without affecting healthy tissues is currently one most active areas research on cancer. The present study focuses a recently proposed approach cell destruction based targeted triggering spontaneous death through mechanical vibration anisotropic magnetic micro/nanoparticles attached membranes at...
Mesothelin (MSLN) is a cell surface glycoprotein overexpressed in several solid malignancies, including gastric, lung, mesothelioma, pancreatic and ovarian cancers. While MSLN-targeting therapeutic approaches are development, only limited efficacy has been achieved patients. A potential shortcoming of described antibody-based that they target the membrane distal region MSLN and, additionally, known to be handicapped by high levels circulating soluble We show here, using monoclonal antibodies...
CD47/SIRPα axis is recognized as an innate immune checkpoint and emerging clinical data validate the interest of interrupting this pathway in cancer, particularly hematological malignancies. In preclinical models, blocking agents have been shown to mobilize phagocytic cells trigger adaptive responses eliminate tumors. Here, we describe mechanisms afforded by a CD47xCD19 bispecific antibody (NI-1701) at controlling tumor growth mouse xenograft B-cell lymphoma model.The contribution effector...
The industrial development of active immunotherapy based on live-attenuated bacterial vectors has matured. We developed a microsyringe for antigen delivery the type III secretion system (T3SS) P. aeruginosa. applied "killed but metabolically active" (KBMA) attenuation strategy to make this vector suitable human use. demonstrate that attenuated aeruginosa potential deliver antigens antigen-presenting cells in vitro via T3SS with considerable cytotoxicity as compared wild-type vector. In mouse...
Live-attenuated bacterial vectors for antigens delivery have aroused growing interest in the field of cancer immunotherapy. Their potency to stimulate innate immunity and promote intracellular antigen into antigen-presenting cells could be exploited elicit a strong specific cellular immune response against tumor cells. We previously described genetically-modified attenuated Pseudomonas aeruginosa able deliver vivo protein cells, through Type 3 secretion system bacteria. Using this approach,...
In contrast to natural antibodies that rely mainly on the heavy chain establish contacts with their cognate antigen, we have developed a bispecific antibody format in which light (LC) drives antigen binding and specificity. To better understand epitope-paratope interactions this context, determined X-ray crystallographic structures of an fragment (Fab) complex human CD47 another Fab PD-L1. These Fabs contain κ-LC λ-LC, respectively, are paired identical (HC). The structural analysis these...
e14016 Background: Many cancers up-regulate the expression of CD47 in order to evade immune surveillance and killing. This 'don't eat me' signal is a molecular means for healthy cells limit their phagocytic elimination by macrophages other innate cells. cell purging mechanism mediated interaction on target Signal Regulatory Protein Alpha (SIRPα) myeloid Development anti-CD47 monoclonal antibodies may be hindered due ubiquitous CD47, leading rapid drug kinetics through target-mediated...
Abstract Upregulation of the immune checkpoint receptor, CD47, on cancer cells promotes evasion and is correlated with poor clinical outcome. CD47 therefore an attractive immuno-oncology target but also a challenging one, given its ubiquitous distribution in healthy tissues. Bispecific antibodies (biAbs) offer superior selectivity as compared to mAbs, they combine two antigen specificities one molecule allowing simultaneous targeting cell surface receptors. We used such dual design create...
e15126 Background: Mesothelin (MSLN) is a cell surface glycoprotein associated with poor prognosis in many cancers, elevated soluble MSLN (sMSLN) serum levels considered biomarker of disease severity. Monoclonal antibodies (mAbs) targeting have demonstrated limited clinical efficacy. CD47, checkpoint for innate immune cells, provides ‘don’t eat me’ signal allowing healthy cells to limit elimination by phagocytes. High CD47 expression correlates yet mAbs blocking are hindered CD47’s...
Abstract The CD47- signal regulatory protein α (SIRPα) axis, originally discovered as a mechanism of self-recognition, has emerged novel innate immune check-point employed by cancer cells to escape surveillance. Over-expression CD47 on plethora hematologic and solid cancers been shown be associated with poor prognosis. blockade is thus considered an attractive strategy retune the host system toward eliminating cells. Clinical efficacy achieved in patients Non-Hodgkin lymphoma (NHL) treated...
Abstract To enhance efficacy of anti-PD-1/PD-L1 antibodies, many combinations with various therapeutic agents are being investigated. Blocking the CD47/SIRPα myeloid checkpoint monoclonal antibodies (mAbs) or decoy receptors is emerging as an effective approach to mobilize dendritic cells and macrophages support T-cell mediated antitumor responses. The benefit combining PD-1/PD-L1 blockade improve tumor control has been convincingly demonstrated in preclinical models now explored patients....
Abstract Mesothelin (MSLN) is a lineage restricted cell surface protein with unknown biological function, expressed at low levels on mesothelial cells in healthy tissue. MSLN also tumor differentiation antigen as it highly across wide range of solid tumors the highest prevalence mesothelioma, pancreatic, biliary, ovarian, lung and gastric cancers. Most hematological cancers upregulate expression CD47, ubiquitous innate immune checkpoint receptor. CD47 interacts signal-regulatory alpha...
<h3>Background</h3> PD-1/PD-L1 blockade can significantly improve survival across many types of cancer, but only in a minority patients. To broaden its therapeutic efficacy, several combination partners are now being evaluated together with blockade. Agents blocking CD47/SIRPα innate immune checkpoint one such example, and co-targeting CD47 monoclonal antibody (mAb) combinations showed increased antitumor responses preclinical studies. However, mAbs hindered by ubiquitous expression leading...
Abstract Up-regulation of CD47 is an immune evasion mechanism used by different cancers to evade surveillance. Through its interaction with signal-regulatory protein alpha (SIRPα) on myeloid cells, delivers a universal “don’t eat me” signal phagocytes, which prevents cells from efficiently eliminating tumor cells. Blockade the SIRPα–CD47 innate checkpoint has therefore emerged as new way treat cancer. Several CD47-targeting molecules are in development encouraging results obtained monoclonal...
The CD47- signal regulatory protein α (SIRPα) axis, originally discovered as a mechanism of self-recognition, has emerged novel innate immune check-point employed by cancer cells to escape surveillance. Over-expression CD47 on plethora hematologic and solid cancers been shown be associated with poor prognosis. blockade is thus considered an attractive strategy retune the host system toward eliminating cells. Clinical efficacy achieved in patients Non-Hodgkin lymphoma (NHL) treated...
Abstract The inhibitory “don't eat me” signal of phagocytosis, CD47, is commonly overexpressed in cancer cells, a feature generally associated with poor prognosis. CD47 overexpression believed to promote immune evasion by allowing tumor cells “hide” from innate phagocytes like macrophages or dendritic cells. therefore new type checkpoint and an attractive target for immunotherapy. However, as also universally expressed on healthy clinical development anti-CD47 monoclonal antibodies...
<p>Supplementary Figure S2 shows in vitro hemagglutination human or cynomolgus monkeys whole blood, platelet aggregation rich-plasma (PRP)in presence of NI-1701</p>