PMID: 9435866Jan 22, 1998Paper

Bispecific Ab therapy of B-cell lymphoma: target cell specificity of antibody derivatives appears critical in determining therapeutic outcome

Cancer Immunology, Immunotherapy : CII
J HoneychurchM J Glennie

Abstract

Despite the success of mAb and bispecific (bs)Ab in the treatment of certain malignancies, there is still considerable uncertainty about the most appropriate format in which they should be used. In the current work we have investigated a panel of bsAb [IgG and F(ab)2] with dual specificity for T cells and neoplastic B cells. Throughout this work, anti-CD2 or anti-CD3 were used to bind the mouse T cells, and antibodies to surface IgM idiotype (Id), CD19, CD22, or MHC class II were used to target mouse B cell lymphomas BCL1 or A31. In vitro, killing was measured in a conventional cytotoxicity assay using 51Cr-labelled A31 and BCL1 cells as targets and activated mouse splenocytes as effectors. bsAb showed a wide range of cytotoxic activities, which could be ranked in the following order: [anti-CD3 x anti-class-II] > [anti-CD3 x anti-CD19] > [anti-CD3 x anti-Id] > [anti-CD3 x anti-CD22], with the [anti-CD2 x anti-Id] derivative showing relatively little cytotoxic activity. This hierarchy of activity indicates some correlation with the binding activity of the bsAb on target cells, but showed a much stronger parallel with the tendency of the anti-(target cells) mAb to undergo antigenic modulation (less modulation, more killing). In v...Continue Reading

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