Characterization of BIS20x3, a bi-specific antibody activating and retargeting T-cells to CD20-positive B-cellsWithoff, S., Bijman, MNA., Stel, AJ., Delahaye, L., Calogero, A., de Jonge, MWA., Kroesen, BJ. & de Leij, L., 20-Apr-2001, In : British Jounal of Cancer. 84, 8, p. 1115-1121 7 p.
Research output: Contribution to journal › Article › Academic › peer-review
This paper describes a bi-specific antibody, which was called BIS20x3. It retargets CD3 epsilon -positive cells (T-cells) to CD20-positive cells and was obtained by hybrid-hybridoma fusion. BIS20x3 could be isolated readily from quadroma culture supernatant and retained all the signalling characteristics associated with both of its chains. Cross-linking of BIS20x3 on Ramos cells leads to DNA fragmentation percentages similar to those obtained after Rituximab-cross-linking. Cross-linking of BIS20x3 on T-cells using cross-linking F(ab')2-fragments induced T-cell activation. Indirect cross-linking of T-cell-bound BIS20x3 via Ramos cells hyper-activated the T-cells. Furthermore, it was demonstrated that BIS20x3 effectively re-targets T-cells to B-cells, leading to high B-cell cytotoxicity. The results presented in this paper show that BIS20x3 is fully functional in retargeting T-cells to B-cells and suggest that B-cell lymphomas may represent ideal targets for T-cell retargeting bi-specific antibodies, because the retargeted T-cell is maximally stimulated in the presence of B-cells. Additionally, since B-cells may up-regulate CD95/Fas expression upon binding of CD20-directed antibodies, B-cells will become even more sensitive for T-cell mediated killing via CD95L/FasL, and therefore supports the intention to use T-cell retargeting bi-specific antibodies recognizing CD20 on B-cell malignancies as a treatment modality for these diseases. (C) 2001 Cancer Research Campaign.
|Number of pages||7|
|Journal||British Jounal of Cancer|
|Publication status||Published - 20-Apr-2001|
- BIS20x3, CD20, rituximab, bi-specific antibody, non-Hodgkin's lymphoma, VARIANT MONOCLONAL-ANTIBODIES, HEAVY-CHAIN ISOTYPE, BISPECIFIC ANTIBODIES, LYMPHOCYTES, APOPTOSIS, LYMPHOMA, CANCER, COSTIMULATION, INDUCTION