Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen.

Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen. Abstract Text:

Yong Tang,Jianlong Lou,R Katherine Alpaugh,Matthew K Robinson,James D Marks,Louis M Weiner,

Unconjugated mAbs have emerged as useful cancer therapeutics. Ab-dependent cellular cytotoxicity (ADCC) is believed to be a major antitumor mechanism of some anticancer Abs. However, the factors that regulate the magnitude of ADCC are incompletely understood. In this study, we described the relationship between Ab affinity and ADCC. A series of human IgG1 isotype Abs was created from the anti-HER2/neu (also named c-erbB2) C6.5 single-chain Fv (scFv) and its affinity mutants. The scFv affinities range from 10(-7) to 10(-11) M, and the IgG Abs retain the affinities of the scFv from which they were derived. The apparent affinity of the Abs ranged from nearly 10(-10) M (the lowest affinity variant) to almost 10(-11) M (the other variants). The IgG molecules were tested for their ability to elicit ADCC in vitro against three tumor cell lines with differing levels of HER2/neu expression using unactivated human PBMC from healthy donors as the effector cells. The results demonstrated that both the apparent affinity and intrinsic affinity of the Abs studied regulate ADCC. High-affinity tumor Ag binding by the IgGs led to the most efficient and powerful ADCC. Tumor cells expressing high levels of HER2/neu are more susceptible to the ADCC triggered by Abs than the cells expressing lower amounts of HER2/neu. These findings justify the examination of high affinity Abs for ADCC promotion. Because high affinity may impair in vivo tumor targeting, a careful examination of Ab structure to function relationships is required to develop optimized therapeutic unconjugated Abs.

Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen. Publishing Authors By Initials

Y Tang,J Lou,RK Alpaugh,MK Robinson,JD Marks,LM Weiner,

For similar proteins: membrane proteins: receptors, cell surface: receptors, immunologic: receptors, fc: receptors, igg research abstracts see: proteins: membrane proteins: receptors, cell surface: receptors, immunologic: receptors, fc: receptors, igg research

PUBMED ID PMID:

MEDLINE DATE:

Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of immunology (Baltimore, Md. : 1950)

VOLUME: 179

Page Numbers: 2815-23

Journal Abbreviation: J. Immunol.

ISSN: 0022-1767

DAY: 1

MONTH: Sep

YEAR: 2007

Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985117

Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen. Keywords Mesh Terms:

KEYWORDS: Receptors, IgG

MESH TERMS: physiology

Chemical & Substance for Abstract: Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen. Information

Substance Name: Receptor, erbB-2

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen.

AFFILIATION: Department of Medical Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA 50633

ACRONYM: CA

MEDLINETA: J Immunol

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen Related Publications

• A randomized clinical trial comparing the effect of maternal intravenous hydration and placebo on the amniotic fluid index in oligohydramnios.
• ADCS Prevention Instrument Project: quality of life assessment (QOL).
• Adapting a dynamic model of interorganizational cooperation to the health care sector.
• Anisotropic Poisson's ratio and compression modulus of cortical bone determined by speckle interferometry.
• Bayesian parallel imaging with edge-preserving priors.
• Binding of mitochondrial leader sequences to Tom20 assessed using a bacterial two-hybrid system shows that hydrophobic interactions are essential and that some mutated leaders that do not bind Tom20 can still be imported.
• Biomechanical properties of the lower uterine segment above and below the reflection of the urinary bladder flap.
• Cardiovascular disease and subsequent kidney disease.
• Caregiving burden responses differ for Internet and telephone data collection.
• Chronic low back pain in older adults: What physicians know, what they think they know, and what they should be taught.
• Cognitive dysfunction in patients with clinically isolated syndromes or newly diagnosed multiple sclerosis.
• Cutting Edge: Immature human dendritic cells express latency-associated peptide and inhibit T cell activation in a TGF-beta-dependent manner.
• Delivery of drugs and macromolecules to mitochondria.
• Different regional patterns of cortical thinning in Alzheimer's disease and frontotemporal dementia.
• Efficacy of novel plasmid DNA encoding vaccinia antigens in improving current smallpox vaccination strategy.
• Electronic health records: high-quality electronic data for higher-quality clinical research.
• Expression of the ammonia transporter, rh C glycoprotein, in normal and neoplastic human kidney.
• How the parallel channels of the retina contribute to depth processing.
• Measurement of hippocampal subfields and age-related changes with high resolution MRI at 4T.
• Plasma 24S hydroxycholesterol response to statins in Alzheimer's disease patients: effects of gender, CYP46, and ApoE polymorphisms.
• Quantitative bioanalytical methods validation and implementation: best practices for chromatographic and ligand binding assays.
• Recovery preference exploration: analysis of patient feedback after imagined scenarios.
• Reengineering CCA-adding enzymes to function as (U,G)- or dCdCdA-adding enzymes or poly(C,A) and poly(U,G) polymerases.
• Regulation of antibody-dependent cellular cytotoxicity by IgG intrinsic and apparent affinity for target antigen.
• Th3 cells in peripheral tolerance. I. Induction of Foxp3-positive regulatory T cells by Th3 cells derived from TGF-beta T cell-transgenic mice.
• Th3 cells in peripheral tolerance. II. TGF-beta-transgenic Th3 cells rescue IL-2-deficient mice from autoimmunity.
• The hairless mouse ear: an in vivo model for studying wound neovascularization.
• The quinone binding site in Escherichia coli succinate dehydrogenase is required for electron transfer to the heme b.
• Voxel-based T2 relaxation rate measurements in temporal lobe epilepsy (TLE) with and without mesial temporal sclerosis.
• X-ray absorption spectroscopic characterization of the molybdenum site of Escherichia coli dimethyl sulfoxide reductase.