In vivo efficacy of the recombinant anti-CD64 immunotoxin H22(scFv)-ETA′ in a human acute myeloid leukemia xenograft tumor model
✍ Scribed by Mehmet Kemal Tur; Michael Huhn; Edgar Jost; Theo Thepen; Tim H. Brümmendorf; Stefan Barth
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- French
- Weight
- 533 KB
- Volume
- 129
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
Abstract
Target‐specific acute myeloid leukemia (AML) immunotherapy requires selective cell‐surface antigens on AML blast cells. CD64 is a promising candidate antigen because it is abundantly expressed on monocytoid differentiated AML subtypes. In previous studies, a chemically linked full‐length anti‐CD64 immunotoxin based on ricin A showed promising results in several animal models, but further development has been hindered by its substantial, dose‐limiting off‐target effects. We recently constructed the recombinant immunotoxin H22(scFv)‐ETA′, comprising a truncated Pseudomonas exotoxin A (PE) and a humanized scFv antibody against CD64. This molecule was shown to kill CD64^+^ AML‐derived tumor cell lines and primary patient‐derived AML cells specifically, both in vitro and ex vivo. Here we describe the in vivo efficiency of H22(scFv)‐ETA′ in the U937/SCID mouse xenograft model for human AML, by providing immunohistochemical evidence for the elimination of human CD64^+^ tumor cells in mouse organs. H22(scFv)‐ETA′ showed potent antitumor activity against myeloid tumor cells and significantly prolonged the overall survival of AML xenograft animals. In conclusion, H22(scFv)‐ETA′ is efficacious against AML with monocytoid differentiation in vitro and in animal models in vivo, providing the basis for a novel therapeutic strategy for the treatment of AML patients.