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Antibodies redirect cytolytic capacity of cytotoxic T lymphocytes.
2004 DEC 1 - (NewsRx.com & NewsRx.net) -- RGD-modified anti-CD3 antibodies redirect cytolytic capacity of cytotoxic T lymphocytes toward alpha[subscript]vbeta[subscript]3-expressing endothelial cells.
"To redirect the lytic activity of cytotoxic T lymphocytes (CTL) toward tumor vascular endothelial cells, we prepared bifunctional proteins with specificity for both alpha[subscript]vbeta[subscript]3 and CD3. Monocyclic RGD peptides (cRGDfK) were covalently coupled to an anti-CD3 monoclonal antibody at different peptide-protein ratios. The resulting RGDpep-anti-CD3 conjugates bound specifically to alpha[subscript]vbeta[subscript]3-expressing endothelial cells," researchers in the Netherlands report.
"Displacement studies with radiolabeled alpha[subscript]vbeta[subscript]3 ligand demonstrated that the alpha[subscript]vbeta[subscript]3 binding affinity of RGDpep-anti-CD3 conjugates was elevated as compared to the non-conjugated RGDpep," stated Astrid J. Schraa and colleagues at the Medical Biology Section and the University Center for Pharmacy in Groningen. "IC[subscript]50 values ranged from 150-1.1 nM, depending on the amount of coupled RGDpep molecules per antibody molecule. RGD modification did not affect the ability of anti-CD3 antibodies to bind to CTL. Furthermore, RGDpep-anti-CD3 was fully capable of activating T cells upon CD3 binding as was shown in a Jurkat/NFAT reporter-gene activation assay."
"All RGDpep-anti-CD3 conjugates were able to induce RGDpep, CD3-dependent lysis of human ...
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Source: HighBeam Research, Antibodies redirect cytolytic capacity of cytotoxic T lymphocytes.