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01.09.2006 | Original Article

The in vitro antitumor effect and in vivo tumor-specificity distribution of human-mouse chimeric antibody against transferrin receptor

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 9/2006

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Abstract

Transferrin receptor (TfR/CD71) deserves attention as a selective target for cancer therapy due to its higher expression in tumors versus normal tissues. Also, it has been shown the mouse-derived monoclonal antibody against TfR can significantly inhibit the proliferation of tumor cells. Through constructing the chimeric antibody against TfR, the antigenicity of antibody can be weakened, and most importantly, the antitumor effect of antibody can be strengthened by the introduction of the human Fc fragment. In previous studies, we successfully constructed the human-mouse chimeric antibody against TfR (D2C) and demonstrated that its Fab fragment could specially recognize the TfR on the surface of target cells. In this study, through labeling the chimeric antibody D2C with ¹²⁵I, we calculated the affinity constant (Ka) of 9.34–9.62×10⁹ l/mol for this antibody according to the Scatchard drawing method. Moreover, in vivo studies in nude mice-bearing human liver cancer (SMMC-7721) xenografts have shown that the radioactivity distribution ratio of ¹³¹I-D2C on T/NT was 2–14:1 or 3–21:1 on the seventh day after intraperitoneal or intratumoral injection of ¹³¹I-labeled D2C (¹³¹I-D2C). These evidences indicated that the in vivo distribution of D2C display the characteristics of certain tumor-specificity localization. In vitro studies, D2C can induce the apoptosis of K562 through the mitochondria death pathway and arrest the cell at G₁ phase, as determined by cell cycle analysis. Using the human tumor cells (K562, CEM, and SMMC-7721) expressing TfR as target cells, and normal human PBMC as effector cells, Fc fragment of D2C can perform both the antibody-dependent cell-mediated cytotoxicity and the complement-dependent cytotoxicity. Together, it was demonstrated that the D2C display a tumor-specificity distribution, and has a strong antitumor effect. Thus, it has the potential therapeutic significance.

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Titel: The in vitro antitumor effect and in vivo tumor-specificity distribution of human-mouse chimeric antibody against transferrin receptor
Publikationsdatum: 01.09.2006
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 9/2006
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-005-0105-7

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Springer Medizin

The in vitro antitumor effect and in vivo tumor-specificity distribution of human-mouse chimeric antibody against transferrin receptor

Abstract

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