Enhanced opsonisation of Rhesus D-positive human red blood cells by recombinant polymeric immunoglobulin G anti-G antibodies.

Background: Anti-RhD antibodies (anti-D) are important in the prophylaxis of haemolytic disease of the foetus and newborn (HDFN) due to RhD incompatibility. Current preparations of anti-D are sourced from hyperimmune human plasma, so its production carries a risk of disease and is dependent on donor availability. Despite the efforts to develop a monoclonal preparation with similar prophylactic properties to the plasma-derived anti-D, no such antibody is yet available.

CTLA4Fcε, a novel soluble fusion protein that binds B7 molecules and the IgE receptors, and reduces human in vitro soluble CD23 production and lymphocyte proliferation.

Immunoglobulin E-mediated allergy and certain autoimmune diseases are characterized by the presence of a T helper type 2 (Th2) immune response and allergen-specific or self-reactive IgE. Soluble CD23 (sCD23) is a B-cell factor that fosters IgE class-switching and synthesis, suggesting that sCD23 may be a therapeutic target for these pathologies. We produced a recombinant protein, CTLA4Fcε, by fusing the ectodomain of the immunoregulatory molecule cytotoxic T-lymphocyte antigen 4 (CTLA-4) with a fragment of the IgE H-chain constant region.

Novel antibody-based proteins for cancer immunotherapy.

The relative success of monoclonal antibodies in cancer immunotherapy and the vast manipulation potential of recombinant antibody technology have encouraged the development of novel antibody-based antitumor proteins. Many insightful reagents have been produced, mainly guided by studies on the mechanisms of action associated with complete and durable remissions, results from experimental animal models, and our current knowledge of the human immune system. Strikingly, only a small percent of these new reagents has demonstrated clinical value.

Decreased survival of human breast cancer cells expressing HER2/neu on in vitro incubation with an anti-HER2/neu antibody fused to C5a or C5a desArg.

Treatment of human epidermal growth factor receptor 2 (HER2/neu)-expressing breast cancer patients with a monoclonal antibody (mAb) directed against HER2/neu improves the outcome of chemotherapy. In cases in which remission is observed, antibody-dependent cell-mediated cytotoxicity (ADCC) seems to be one of the main mechanisms of anti-HER2/neu mAb action, implicating Fc gamma receptors (Fc gamma Rs) in this tumoricidal activity. In vitro and in vivo studies have revealed that anti-HER2/neu-mediated ADCC is mainly accomplished by polymorphonuclear granulocytes (PMN).

Recombinant polymeric IgG anti-Rh: a novel strategy for development of direct agglutinating reagents.

Anti-Rh alloantibodies are used in research and clinic laboratories to define the Rh antigenic profile of human blood samples. IgM anti-Rh antibodies directly agglutinate Rh-positive RBCs. Anti-Rh antibodies of the IgG isotype bind to Rh antigens with a higher intrinsic affinity than IgM and sensitize RBCs, but do not induce direct hemagglutination.

[A and B blood group-specific monoclonal antibodies. Production and evaluation as ABO-blood typing reagents].

The Monoclonal Antibody (MoAb) technology has been successfully applied to develop reagents for human blood group classification. There is no production of this kind of reagents in Venezuela, and the local demand (blood banks and clinical laboratories) is mainly supplied with imported material. Considering this we decided to apply MoAb techniques to generate murine hybridomas secreting anti-A or anti-B specific MoAb.

Risk of adverse post-transplant events after kidney allograft transplantation as predicted by CTLA-4 +49 and TNF-alpha -308 single nucleotide polymorphisms: a preliminary study.

Genetic differences between donor and recipient HLA haplotypes are of major importance for transplant rejection. Other genetic variations occurring in genes encoding cytokines and costimulatory molecules also appear to exert an influence on the manner the host immune system recognizes the allograft. The aims of this work were: 1) to study selected single nucleotide polymorphisms (SNPs) at the loci encoding the T-cell regulatory molecule CTLA-4 (CD152), and the cytokines interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and transforming growth factor (TGF)-beta1 in a sample of healthy volunteers and a group of kidney-transplanted patients; and 2) to investigate whether an association exists between any of the SNPs studied and acute or chronic rejection, or non-responsiveness to steroid treatment during episodes of acute rejection (AR) after kidney allograft transplantation.

Influence of the isotype of the light chain on the properties of IgG.

It is widely appreciated that the isotype of the H chain of the Ab molecule influences its functional properties. We have now investigated the contribution of the isotype of the L chain to the structural and functional properties of the Ab molecule. In these studies, the L chain variable region of a murine anti-dansyl Ab was joined to either human kappa or lambda constant region domains and expressed with mouse-human chimeric H chains of the four human IgG isotypes.