Bispecific antibodies reactive with the multidrug-resistance-related glycoprotein and CD3 induce lysis of multidrug-resistant tumor cells
✍ Scribed by J. van Dijk; T. Tsuruo; D. M. Segal; R. L. H. Bolhuis; R. Colognola; R. J. van de Griendleuren; G. J. Fleuren; S. O. Warnaar
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- French
- Weight
- 620 KB
- Volume
- 44
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
We describe the lysis of multidrug-resistant (MDR) tumor cells by various lymphocytic effector cells, retargeted with bispecific antibodies (heteroconjugates). The Ab
-heteroconjugate used was prepared by chemically cross-linking the OKT3 monoclonal antibody (MAb) reactive with CD3 antigen on T lymphocytes, with the MRKl6 MAb, which recognizes the MDR-associated P-glycoprotein. Cloned TCRafj/CD3+ T lymphocytes, OKT3-activated peripheral-blood mononuclear cells and peripheral-blood mononuclear blood lymphocytes, stimulated with allogeneic irradiated cells in a mixed lymphocyte culture, could be induced to lyse MDR ovarian tumor cells in the presence of Ab-heteroconjugate CD3/MRKI 6, whereas the drug-sensitive parental tumor cells lacking the P-glycoprotein were not lysed by these retargeted effector cells. Cloned TCRyfi/CD3+ T lymphocytes showed a high MHC-unrestricted lysis of MDR tumor cells. Addition of Abheteroconjugate CD3/MRK16 could therefore not enhance target-cell Iysis. Melanoma tumor cells transfected with the m d ~l gene which codes for the P-glycoprotein were also efficiently lysed by Ab-heteroconjugate retargeted cloned TCRafj/CD3' T cells. Tumor cell lines derived from organs known to express the P-glycoprotein also were lysable by the retargeted effector cells.