A5015493591- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- Nanoparticle-Based Drug Delivery
- Immunotherapy and Immune Responses
- Nanoplatforms for cancer theranostics
- Radiopharmaceutical Chemistry and Applications
- Tea Polyphenols and Effects
- Toxin Mechanisms and Immunotoxins
- Viral Infections and Immunology Research
- Cancer Cells and Metastasis
- Rheumatoid Arthritis Research and Therapies
- Bioactive Compounds in Plants
- Antioxidant Activity and Oxidative Stress
- Herpesvirus Infections and Treatments
- Muscle Physiology and Disorders
- vaccines and immunoinformatics approaches
- Exercise and Physiological Responses
- Sirtuins and Resveratrol in Medicine
- Cancer, Stress, Anesthesia, and Immune Response
- Cytomegalovirus and herpesvirus research
- Graphene research and applications
- Surface and Thin Film Phenomena
- HIV Research and Treatment
- Cervical Cancer and HPV Research
Genmab (Netherlands)
2022-2024
University of Rome Tor Vergata
2024
University of Florence
2013-2022
Queen Mary University of London
2014
Universitat de Barcelona
2010-2012
Stanford University
1998
National Institutes of Health
1995
Abstract Checkpoint inhibitors (CPI) have revolutionized the treatment paradigm for advanced solid tumors; however, there remains an opportunity to improve response rates and outcomes. In preclinical models, 4-1BB costimulation synergizes with CPIs targeting programmed cell death protein 1 (PD-1)/programmed ligand (PD-L1) axis by activating cytotoxic T-cell–mediated antitumor immunity. DuoBody-PD-L1×4-1BB (GEN1046) is investigational, first-in-class bispecific immunotherapy agent designed...
hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of pancreatic ductal adenocarcinoma (PDAC) is lacking. expression was tested PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). studied cell lines cultures. ERG1 during progression Pdx-1-Cre,LSL-KrasG12D/+,LSL-Trp53R175H/+ transgenic (KPC) mice. vivo determined optical imaging Alexa-680-labelled...
We previously demonstrated that a single-chain fragment variable (scFv) specific to collagen type II (CII) posttranslationally modified by reactive oxygen species (ROS) can be used target anti-inflammatory therapeutics specifically inflamed arthritic joints. The objective of the present study was demonstrate superior efficacy cytokines when targeted joints anti-ROS CII (anti-ROS-CII) scFv in mouse model arthritis. Viral interleukin-10 (vIL-10) fused anti-ROS-CII (1-11E) with...
Titanium dioxide (TiO2) has been widely used in many nanotechnology areas including nanomedicine, where it could be proposed for the photodynamic and sonodynamic cancer therapies. However, TiO2 nanoformulations have shown to toxic living cells. In this article, we report development of a new delivery system, based on nontoxic nanoparticles, further conjugated with monoclonal antibody against novel easily accessible tumor marker, e.g., Kv 11.1 potassium channel. We synthesized, by simple...
Modern molecular imaging techniques have greatly improved tumor detection and post-treatment follow-up of cancer patients. In this context, antibody-based is rapidly becoming the gold standard, since it combines unique specificity antibodies with sensitivity different technologies. The aim study was to generate characterize in single chain Fragment variable (scFv) format directed an emerging biomarker, human ether-à-go-go-related gene-1 (hERG1) potassium channel, obtain a proof concept for...
Abstract Background Improving cancer immunotherapy long-term clinical benefit is a major priority. It has become apparent that multiple axes of immune suppression restrain the capacity T cells to provide anti-tumour activity including signalling through PD1/PD-L1 and LAG3/MHC-II. Methods CB213 been developed as fully human PD1/LAG3 co-targeting multi-specific Humabody composed linked V H domains avidly bind block PD1 LAG3 on dual-positive cells. We present preclinical primary pharmacology...
The aim of the present investigation was to examine anti-wasting effects theophylline (a methylxantine in tea leaves) on a rat model cancer cachexia. vitro nutraceuticals proteolysis were examined muscle cell cultures submitted hyperthermia. Individual weights, gene expression, body composition and cardiac function measured rats bearing Yoshida AH-130 ascites hepatoma, following treatment. Theophylline treatment inhibited C2C12 line resulted an anti-proteolytic effect tissue (soleus heart),...
The effect of patient preimmunization virus sequences on CTL responses during gp160 immunization were studied. Ten HLA-A2+, HIV+ asymptomatic patients with CD4+ T cells >500/mm3 given two courses HIV-1 MN rgp160 vaccine over a 2-year period. Envelope epitope-specific responses, using PBMCs, measured against peptide-coated autologous B lymphoblastoid cell lines. Optimum epitopes determined by HLA-A2-binding affinity 9- to 10-mer peptides containing the HLA-A2.1-binding motif. high- or...
Abstract Introduction: Chronic antigen stimulation is known to promote a state of T cell dysfunction whereby cells are unable mount effector responses such as cytokine release, proliferation and tumour killing. Indeed, dysfunctional found be located within the microenvironment where they express high levels inhibitory receptors LAG3 PD-1 on their surface. Targeting tumoral re-invigoration functions an attractive strategy for combatting intrinsic acquired resistance current checkpoint...
<h3>Background</h3> Acasunlimab (DuoBody®-PD-L1x4-1BB) is an investigational, bispecific antibody (bsAb) designed to elicit anti-tumor immune responses via conditional 4-1BB activation that strictly dependent on simultaneous PD-L1 binding.<sup>1</sup> Pharmacokinetic/pharmacodynamic evidence previously demonstrated doses of acasunlimab allow optimal stimulation result in partial blockade.<sup>2</sup> Preclinical studies showed combining with anti-PD-1 elicits durable by allowing and complete...
<div>Abstract<p>Checkpoint inhibitors (CPI) have revolutionized the treatment paradigm for advanced solid tumors; however, there remains an opportunity to improve response rates and outcomes. In preclinical models, 4-1BB costimulation synergizes with CPIs targeting programmed cell death protein 1 (PD-1)/programmed ligand (PD-L1) axis by activating cytotoxic T-cell–mediated antitumor immunity. DuoBody-PD-L1×4-1BB (GEN1046) is investigational, first-in-class bispecific...
<div>Abstract<p>Checkpoint inhibitors (CPI) have revolutionized the treatment paradigm for advanced solid tumors; however, there remains an opportunity to improve response rates and outcomes. In preclinical models, 4-1BB costimulation synergizes with CPIs targeting programmed cell death protein 1 (PD-1)/programmed ligand (PD-L1) axis by activating cytotoxic T-cell–mediated antitumor immunity. DuoBody-PD-L1×4-1BB (GEN1046) is investigational, first-in-class bispecific...
Supplementary Figure from Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors
Supplementary Figure from Preclinical Characterization and Phase I Trial Results of a Bispecific Antibody Targeting PD-L1 4-1BB (GEN1046) in Patients with Advanced Refractory Solid Tumors
Abstract GEN1046 (DuoBody®-PD-L1x4-1BB) is an investigational, potential first-in-class bispecific immunomodulatory antibody designed to elicit anti-tumor immune response by simultaneous and complementary blockade of PD-L1 on tumor or cells conditional 4-1BB stimulation T NK cells. Previously, we described encouraging preclinical early clinical activity (Muik, et al., 2022, Cancer Discovery). We hypothesized that combining with PD-1 would further potentiate through distinct modulatory...
<h3>Background</h3> GEN1042 (DuoBody<sup>®</sup>-CD40x4–1BB) is an investigational, novel, bispecific antibody that combines targeting and conditional activation of CD40 4–1BB on immune cells. We recently reported preclinical characterization encouraging clinical activity in solid tumors.<sup>1 2</sup> Here, we investigated <i>in vivo</i> biological mechanism action using the mouse-human chimeric, Fc-inert, surrogate GEN1042-mIgG2a immunocompetent human CD40/human double knock-in...
Abstract Agonistic monoclonal antibodies targeting CD137/4-1BB have shown much preclinical promise but their clinical development has been slowed due to a poor therapeutic index, in particular liver toxicity. CB307 is novel half-life extended bispecific Humabody VH CD137 (4-1BB) and prostate specific membrane antigen (PSMA). The design of enables agonism selectively the presence PSMA positive tumour cells this way enable selective T cell activation whilst minimising systemic activation....