Different types of FC γ -receptors are involved in anti-Lewis Y antibody induced effector functions in vitro

Stimulation of monocytes by interaction of monoclonal antibodies (mAbs) with Fc gamma receptors (FcγRs) results in the activation of various monocyte effector functions. In the present investigation we show that the anti-Lewis Y (LeY) anti-tumour mAb ABL 364 and its mouse/human IgG1 chimaera induce both antibody-dependent cellular cytotoxicity (ADCC) and the release of tumour necrosis factor α (TNF-α) during mixed culture of monocytes with LeY+SKBR5 breast cancer cells in vitro. Although anti-LeY mAb-mediated TNF-α release paralleled ADCC activity, cytokine release required a higher concentration of sensitizing mAb than the induction of cytolysis. The determination of the FcγR classes involved in the induction of the distinct effector functions showed that anti-LeY mAb-induced cytolysis was triggered by interaction between anti-LeY mAbs and FcγRI. In contrast, mAb-induced TNF-α release mainly depended on the activation of monocyte FcγRII. Neutralization of TNF-α showed no influence on monocyte ADCC activity towards SKBR5 target cells. Our data indicate an independent regulation of anti-LeY mAb induced effector functions of ADCC and TNF-α release which seemed to be triggered by activation of different types of FcγR. © 2000 Cancer Research Campaig

Importance of ligand conformational energies in carbohydrate docking: sorting the wheat from the chaff

Docking algorithms that aim to be applicable to a broad range of ligands suffer reduced accuracy because they are unable to incorporate ligand-specific conformational energies. Here, we develop internal energy functions, Carbohydrate Intrinsic (CHI), to account for the rotational preferences of the glycosidic torsion angles in carbohydrates. The relative energies predicted by the CHI energy functions mirror the conformational distributions of glycosidic linkages determined from a survey of oligosaccharide-protein complexes in the Protein Data Bank. Addition of CHI energies to the standard docking scores in Autodock 3, 4.2, and Vina consistently improves pose ranking of oligosaccharides docked to a set of anti-carbohydrate antibodies. The CHI energy functions are also independent of docking algorithm, and with minor modifications, may be incorporated into both theoretical modeling methods, and experimental NMR or X-ray structure refinement programs