Search results for "Humanized"

DOTAGA-Trastuzumab. A New Antibody Conjugate Targeting HER2/Neu Antigen for Diagnostic Purposes.

2012

International audience; Improved bifunctional chelating agents (BFC) are required for indium-111 radiolabeling of monoclonal antibodies (mAbs) under mild conditions to yield stable, target-specific agents. 2,2',2″-(10-(2,6-Dioxotetrahydro-2H-pyran-3-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetic acid (DOTAGA-anhydride) was evaluated for mAb conjugation and labeling with indium-111. The DOTA analogue was synthesized and conjugated to trastuzumab-which targets the HER2/neu receptor-in mild conditions (PBS pH 7.4, 25 °C, 30 min) and gave a mean degree of conjugation of 2.6 macrocycle per antibody. Labeling of this immunoconjugate with indium-111 was performed in 75% yield after 1 h a…

2015

Regulatory T cells (Treg) control immune cell function as well as non-immunological processes. Their far-reaching regulatory activities suggest their functional manipulation as a means to sustainably and causally intervene with the course of diseases. Preclinical tools and strategies are however needed to further test and develop interventional strategies outside the human body. "Humanized" mouse models consisting of mice engrafted with human immune cells and tissues provide new tools to analyze human Treg ontogeny, immunobiology, and therapy. Here, we summarize the current state of humanized mouse models as a means to study human Treg function at the molecular level and to design strategie…

Ramucirumab and its use in gastric cancer treatment

2014

Abstract: The inhibition of the mechanisms of tumor neo-angiogenesis represents a milestone that in the last 10 years has seen the advent of numerous molecules to target action against the vascular endothelial growth factor (VEGF). More recently, new molecules have been developed that inhibit tumor spread by the blockade of specific VEGF receptors (VEGFRs), thereby preventing the binding of a ligand to its receptor and the cascade of proliferative events downstream. Ramucirumab is a fully humanized IgG1 monoclonal antibody that performs its action by blocking the isoform 2 of the VEGF receptor (VEGFR-2). Numerous preclinical and clinical studies have demonstrated its activity in several sol…

Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patien…

2015

OBJECTIVE: To compare lipid-lowering efficacy of adding alirocumab to rosuvastatin versus other treatment strategies (NCT01730053).METHODS: Patients receiving baseline rosuvastatin regimens (10 or 20 mg) were randomized to: add-on alirocumab 75 mg every-2-weeks (Q2W) (1-mL subcutaneous injection via pre-filled pen); add-on ezetimibe 10 mg/day; or double-dose rosuvastatin. Patients had cardiovascular disease (CVD) and low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dL (1.8 mmol/L) or CVD risk factors and LDL-C ≥100 mg/dL (2.6 mmol/L). In the alirocumab group, dose was blindly increased at Week 12 to 150 mg Q2W (also 1-mL volume) in patients not achieving their LDL-C target. Primary endpoi…

Reply to: Safety and efficacy of secukinumab treatment in a patient with ankylosing spondylitis and concomitant multiple sclerosis: A commentary

2021

No abstract available

A phase I/II trial of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab as first-line treatment in HER-2-positive locally advanced or me…

2011

Abstract Aim To assess the activity and safety of non-pegylated liposomal doxorubicin (Myocet®) in combination with docetaxel and trastuzumab as first-line treatment of patients with HER-2/neu-positive metastatic breast cancer (MBC). Patients and methods The maximum tolerated dose of the combination was defined in the phase I part of the study. In the phase II part, 45 HER-2/neu-positive MBC patients were enrolled to receive 6–8 cycles of Myocet® 50 mg/m2 (day 1), docetaxel 30 mg/m2 (days 2 and 9) plus trastuzumab (day 2, 4 mg/kg followed by 2 mg/kg/week) every 21 d until unacceptable toxicity or progression occurred. Objective response (primary end-point) and treatment tolerability were as…

Safety and clinical activity of a combination therapy comprising two antibody-based targeting agents for the treatment of non-Hodgkin lymphoma: resul…

2013

Purpose Inotuzumab ozogamicin (INO) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. We performed a phase I/II study to determine the maximum-tolerated dose (MTD), safety, efficacy, and pharmacokinetics of INO plus rituximab (R-INO) for treatment of relapsed/refractory CD20+/CD22+ B-cell non-Hodgkin lymphoma (NHL). Patients and Methods A dose-escalation phase to determine the MTD of R-INO was followed by an expanded cohort to further evaluate the efficacy and safety at the MTD. Patients with relapsed follicular lymphoma (FL), relapsed diffuse large B-cell lymphoma (DLBCL), or refractory aggressive NH…

Safety and Pharmacokinetics/Pharmacodynamics of the First-in-Class Dual Action HER3/EGFR Antibody MEHD7945A in Locally Advanced or Metastatic Epithel…

2015

Abstract Purpose: The novel dual-action humanized IgG1 antibody MEHD7945A targeting HER3 and EGFR inhibits ligand-dependent HER dimer signaling. This phase I study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of MEHD7945A. Experimental Design: Patients with locally advanced or metastatic epithelial tumors received escalating doses of MEHD7945A (1–30 mg/kg) every 2 weeks (q2w) until disease progression or intolerable toxicity. An expansion cohort was enrolled at the recommended phase II dose (14 mg/kg, q2w). Plasma samples, tumor biopsies, FDG-PET were obtained for assessment of pharmacokinetics, and pharmacodynamic modulation downstream of EGFR and HER3. …

Phase II trial of bevacizumab and dose/dense chemotherapy with cisplatin and metronomic daily oral etoposide in advanced non-small-cell-lung cancer p…

2011

Bevacizumab, is a humanized monoclonal antibody to vasculo-endothelial- growth-factor, with anticancer activity in non-small-cell-lung cancer (NSCLC) patients. Our previous results from a dose/finding phase I trial in NSCLC patients, demonstrated the anti-angiogenic effects and toxicity of a newest bevacizumab-based combination with fractioned cisplatin and daily oral etoposide. We designed a phase II trial to evaluate in advanced NSCLC patients the antitumor activity and the safety of this novel regimen. In particular, 45 patients (36 males and 9 females), with a mean age of 54 years, an ECOG ≤2, stage III B/IV and NSCLC (28 adenocarcinomas, 11 squamous-cell carcinomas, 2 large-cell carcin…

Cigarette smoking habit does not reduce the benefit from first line trastuzumab-based treatment in advanced breast cancer patients.

2011

Many ErbB2-positive cancers may show intrinsic resistance, and the frequent development of acquired resistance to ErbB-targeted agents represents a substantial clinical problem. The constitutive NF-κB activation in some HER-2/neu positive breast cancer may represent a potential cause of resistance to trastuzumab therapy. Preclinical data revealed that 4-(N-Methyl-N- nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), the tobacco-specific nitrosamine is able to enhance NF-κB DNA binding activity and theoretically to increase the resistance to trastuzumab. Two hundred and forty-eight women with pathologically confirmed, uni- or bidimensionally measurable, HER-2-positive metastatic breast cancer (MBC…