Targeting ErbB2 and ErbB3 with a bispecific single-chain Fv enhances targeting selectivity and induces a therapeutic effect in vitro.

Inappropriate signalling through the EGFR and ErbB2/HER2 members of the epidermal growth factor family of receptor tyrosine kinases is well recognised as being causally linked to a variety of cancers. Consequently, monoclonal antibodies specific for these receptors have become increasingly important components of effective treatment strategies for cancer. Increasing evidence suggests that ErbB3 plays a critical role in cancer progression and resistance to therapy.

Isolation of anti-MISIIR scFv molecules from a phage display library by cell sorter biopanning.

While cell surface antigens represent the most common targets for antibody-based cancer therapy, isolation of new antibodies specific for these targets from single-chain Fv phage display libraries has been hindered by limitations associated with traditional selection techniques. Solid phase panning is often associated with conformational changes to the target protein due to its immobilization on plastic tubes that can limit the ability of the isolated scFv to bind to conformational epitopes and solution panning methods require the use of secondary tags that often mask desired sequences and create unintended epitopes. Commonly utilized cell-based panning methods typically yield a panel of single-chain Fv (scFv) molecules that are specific for numerous cell surface antigens, often obscuring the desired clones.

Development of engineered antibodies specific for the Müllerian inhibiting substance type II receptor: a promising candidate for targeted therapy of ovarian cancer.

The Müllerian inhibiting substance type II receptor (MISIIR) is involved in Müllerian duct regression as part of the development of the male reproductive system. In adult females, MISIIR is present on ovarian surface epithelium and is frequently expressed on human epithelial ovarian cancer cells. Müllerian inhibiting substance has been found to be capable of inhibiting the growth of primary human ovarian cancer cells derived from ascites and ovarian cancer cell lines.

Isolation of scFvs to in vitro produced extracellular domains of EGFR family members.

The members of the epidermal growth factor receptor (EGFR) family are over expressed in a variety of malignancies and are frequently linked to aggressive disease and a poor prognosis. Although clinically effective monoclonal antibodies (MAbs) have been developed to target HER2 and EGFR, the remaining two family members, HER3 and HER4, have not been the subject of significant efforts. In this paper, we have taken the initial steps required to generate antibodies with potential clinically utility that target the members of the EGFR family.

Radioimmunotherapy with engineered antibodies.

Although the advent of monoclonal antibody technology in the 1970s provided the means to specifically target radioisotopes to tumours, the initial clinical evaluations of radioimmunotherapy (RAIT) were largely unsuccessful. Over the past few decades, molecular biology techniques have advanced sufficiently to allow scientists to re-engineer antibodies to address the factors that were believed to be responsible for the failures of the early radioimmunotherapy trials. This review addresses the recent advances in antibody engineering and in RAIT strategies that have brought this field to the brink of success.

Prevalence of factor V Leiden and prothrombin 20210 A variant in Bulgarian patients with pulmonary thromboembolism and deep venous thrombosis.

Factor V Leiden mutation and prothrombin variant 20210 A are well-known risk factors for venous thrombosis (DVT). Recent papers have reported a lower prevalence of factor V Leiden in patients with pulmonary thromboembolism (PTE) than in patients with deep venous thrombosis. The aim of the present study was to compare the prevalence of factor V Leiden and the prothrombin 20210 G <-- A mutation in patients with DVT and in patients with PTE.

Tpl-2 induces apoptosis by promoting the assembly of protein complexes that contain caspase-9, the adapter protein Tvl-1, and procaspase-3.

The Tpl-2 proto-oncoprotein promotes cellular proliferation when overexpressed in a variety of tumor cell lines. Here, we present evidence that when overexpressed in immortalized non-transformed cells, Tpl-2 induces apoptosis by promoting the activation of caspase-3 via a caspase-9-dependent mechanism, and that apoptosis is enhanced when Tpl-2 is co-expressed with the newly identified ankyrin repeat protein Tvl-1. The activation of caspase-3 by caspase-9 is known to depend on the assembly of a multimolecular complex that includes Apaf-1 and caspase-9.

Protein C activity in patients with antiphospholipid syndrome.

The interaction between antiphospholipid antibodies and the protein C system may explain at least a part of the mechanisms underlying thrombosis in the antiphospholipid syndrome (APS). We evaluated the protein C activity, factor V Leiden mutation and the presence of several types of antiphospholipid antibodies in 60 patients with antiphospholipid syndrome. Nineteen patients (31.