Antibody engineering.

G P Winter

doi:10.1098/rstb.1989.0066

Home/Archive/PubMed

PubMed · 2573089

Antibody engineering.

G P Winter

View original source ↗Export metadata ↓

Abstract

The antibody molecule is a therapeutic agent, designed by nature to bind to a wide range of antigen molecules and to trigger effector functions, such as complement lysis and cell-mediated killing. The genes encoding antibodies can be manipulated in vitro, allowing the binding sites for antigen and effector molecules to be dissected, and new properties to be engineered. The future for the application of engineered antibodies in medicine is reviewed in the context of the past century.

Explore related subjects

Antibodies Antibodies, Monoclonal Computer Graphics Genes, Immunoglobulin Genetic Engineering Humans Immunotherapy Models, Structural Protein Conformation Journal Article Review

Keep this discovery

Explore connections, maps & timelines

BibTeX RIS

G P Winter. 1989-08-31. Antibody engineering.. https://doi.org/10.1098/rstb.1989.0066

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2021

ERBB3 overexpression due to miR-205 inactivation confers sensitivity to FGF, metabolic activation, and liability to ERBB3 targeting in glioblastoma.

In glioblastoma (GBM), the most frequent and lethal brain tumor, therapies suppressing recurrently altered signaling pathways failed to extend survival. However, in patient subsets, specific genetic lesions can confer sensitivity to targeted agents. By exploiting an integrated model based on patient-derived stem-like cells, faithfully recapitulating the original GBMs in vitro and in vivo, here, we identify a human GBM subset (∼9% of all GBMs) characterized by ERBB3 overexpression and nuclear accumulation. ERBB3 overexpression is driven by inheritable promoter methylation or post-transcriptional silencing of the oncosuppressor miR-205 and sustains the malignant phenotype. Overexpressed ERBB3 behaves as a specific signaling platform for fibroblast growth factor receptor (FGFR), driving PI3K/AKT/mTOR pathway hyperactivation, and overall metabolic upregulation. As a result, ERBB3 inhibition by specific antibodies is lethal for GBM stem-like cells and xenotransplants. These findings highlight a subset of patients eligible for ERBB3-targeted therapy.

Antibodies↗

PubMed2001

Proteasome inhibitors sensitize human vascular smooth muscle cells to Fas (CD95)-mediated death.

It was investigated whether proteasome activity was implicated in susceptibility of human vascular smooth muscle cells (VSMCs) to Fas-mediated death. Human fetal aorta smooth muscle cells were treated with agonistic anti-Fas antibody (CH11) and proteasome inhibitors (MG115 or MG132) and then cell death was determined by morphology, viability, and DNA fragmentation. The present study reports that: (a) crosslinking of Fas receptor with anti-Fas antibody in the presence of proteasome inhibitor-induced death and DNA degradation in human VSMCs that were blocked by caspases inhibitor z-DEVD.fmk; (b) cotreatment with anti-Fas antibody and proteasome inhibitor activated caspase-3; (c) proteasome inhibitors did not influence expression of procaspase-8, procaspase-3, c-FLIP, and Bcl-2; and (d) proteasome inhibitors up-regulated Fas and FADD. The data indicate that proteasome activity is important in survival of VSMCs and provide the first evidence that proteasome is involved in Fas signal transduction. The present study proposes novel mechanism(s) by which VSMCs become susceptible to FasL.

Antibodies↗

PubMed2001

Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study.

OBJECTIVE: To investigate the association between early childhood infections and subsequent development of asthma. DESIGN: Longitudinal birth cohort study. SETTING: Five children's hospitals in five German cities. PARTICIPANTS: 1314 children born in 1990 followed from birth to the age of 7 years. MAIN OUTCOME MEASURES: Asthma and asthmatic symptoms assessed longitudinally by parental questionnaires; atopic sensitisation assessed longitudinally by determination of IgE concentrations to various allergens; bronchial hyperreactivity assessed by bronchial histamine challenge at age 7 years. RESULTS: Compared with children with </=1 episode of runny nose before the age of 1 year, those with >/=2 episodes were less likely to have a doctor's diagnosis of asthma at 7 years old (odds ratio 0.52 (95% confidence interval 0.29 to 0.92)) or to have wheeze at 7 years old (0.60 (0.38 to 0.94)), and were less likely to be atopic before the age of 5 years. Similarly, having >/=1 viral infection of the herpes type in the first 3 years of life was inversely associated with asthma at age 7 (odds ratio 0.48 (0.26 to 0.89)). Repeated lower respiratory tract infections in the first 3 years of life showed a positive association with wheeze up to the age of 7 years (odds ratio 3.37 (1.92 to 5.92) for >/=4 infections v </=3 infections). CONCLUSION: Repeated viral infections other than lower respiratory tract infections early in life may reduce the risk of developing asthma up to school age.

Antibodies↗