Effective elimination of acute myeloid leukemic cells by recombinant bispecific antibody derivatives directed against CD33 and CD16.
Singer H, Kellner C, Lanig H, Aigner M, Stockmeyer B, Oduncu FS, Schwemmlein M, Stein C, Mentz K, Mackensen A, Fey G (2010)
Publication Language: English
Publication Status: Published
Publication Type: Journal article, Original article
Publication year: 2010
Journal
Book Volume: 33
Pages Range: 599-608
Journal Issue: 6
DOI: 10.1097/CJI.0b013e3181dda225
Abstract
Single-chain Fv triplebodies (sctb), consisting of a single polypeptide chain with 3 single-chain antibody variable fragments connected in tandem, were generated as antileukemic agents. A CD19-specific sctb of this format has previously been shown to be superior to a bispecific single-chain Fv antibody fragment (bsscFv) for the elimination of leukemic B-lineage cells, but corresponding targeted agents for the treatment of acute myeloid leukemia are still lacking. For this purpose, both a bsscFv and a sctb specific for CD33 and the trigger molecule CD16 (FcgammaRIII) were produced. The sctb displayed 3.5-fold greater avidity for CD33 than the bsscFv 33xds16, whereas both had close to equal affinity for CD16. In antibody-dependent cellular cytotoxicity (ADCC) reactions with human mononuclear cells as effectors, both the bsscFv 33xds16 and the sctb induced lysis of tumor cells with half maximum effective concentrations (EC50) in the low picomolar range. It is interesting to note that the sctb promoted equal lysis of human leukemia-derived cell lines at 10 to 200-fold lower concentrations than the bsscFv. Both molecules mediated ADCC of primary patient cells. In conclusion, both the bsscFv 33xds16 and the sctb 33xds16x33 eliminated acute myeloid leukemia cells in ADCC reactions, but the novel sctb format showed significantly greater specific activity.
Authors with CRIS profile
Harald Lanig
Zentralinstitut für Scientific Computing (ZISC)
Andreas Mackensen
Lehrstuhl für Innere Medizin V
Georg Fey
Naturwissenschaftliche Fakultät
Involved external institutions
Germany (DE)How to cite
APA:
Singer, H., Kellner, C., Lanig, H., Aigner, M., Stockmeyer, B., Oduncu, F.S.,... Fey, G. (2010). Effective elimination of acute myeloid leukemic cells by recombinant bispecific antibody derivatives directed against CD33 and CD16. Journal of Immunotherapy, 33(6), 599-608. https://dx.doi.org/10.1097/CJI.0b013e3181dda225
MLA:
Singer, Heiko, et al. "Effective elimination of acute myeloid leukemic cells by recombinant bispecific antibody derivatives directed against CD33 and CD16." Journal of Immunotherapy 33.6 (2010): 599-608.
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