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In vivo efficacy of the recombinant anti-CD64 immunotoxin H22(scFv)-ETA in a human acute myeloid leukemia xenograft tumor model

: Tur, M.K.; Huhn, M.; Jost, E.; Thepen, T.; Brümmendorf, T.H.; Barth, S.


International journal of cancer 129 (2011), Nr.5, S.1277-1282
ISSN: 0020-7136
ISSN: 1097-0215
Fraunhofer IME ()

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 i n 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.