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.
journal_name
Int J Cancerjournal_title
International journal of cancerauthors
Tur MK,Huhn M,Jost E,Thepen T,Brümmendorf TH,Barth Sdoi
10.1002/ijc.25766subject
Has Abstractpub_date
2011-09-01 00:00:00pages
1277-82issue
5eissn
0020-7136issn
1097-0215journal_volume
129pub_type
杂志文章abstract::Although early detection and systemic therapies have improved the diagnosis and clinical cure rate of breast cancer, breast cancer remains the most frequently occurring malignant cancer in women due to a lack of sufficiently effective treatments. Thus, to develop potential targeted therapies and thus benefit more pati...
journal_title:International journal of cancer
pub_type: 杂志文章
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abstract::Nasopharyngeal carcinoma is an Epstein-Barr Virus (EBV) associated malignancy which is highly prevalent in Southeast Asia. EBV-related antibodies have been widely used as screening markers for early nasopharyngeal carcinoma (NPC) detection. However, due to its low positive predictive rate, it is essential to develop n...
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journal_title:International journal of cancer
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abstract::Apoptin is a chicken anemia virus-derived, p53-independent, bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis in tumor cells. To explore the use of the Apoptin gene in cancer gene therapy, we constructed a recombinant fowlpox virus expressing the Apoptin protein (vFV-Apoptin) and co...
journal_title:International journal of cancer
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abstract::A human revertant cell line, derived from non-producer human osteosarcoma cells (NP/KHOS) induced by Kirsten murine sarcoma virus, was treated in vitro with various levels of polycyclic aromatic hydrocarbons (3-methylcholanthrene, 7,12-dimethylbenz(alpha)anthracene, and benzo(alpha)pyrene [BP] or dimethyl sulfoxide (c...
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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journal_title:International journal of cancer
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