Humanization of the bispecific epidermal growth factor receptor x CD3 diabody and its efficacy as a potential clinical reagent.

Humanization of the bispecific epidermal growth factor receptor x CD3 diabody and its efficacy as a potential clinical reagent. Research Abstract Details 

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Humanization of the bispecific epidermal growth factor receptor x CD3 diabody and its efficacy as a potential clinical reagent. Abstract Text:

Ryutaro Asano,Yukiko Sone,Koki Makabe,Kouhei Tsumoto,Hiroki Hayashi,Yu Katayose,Michiaki Unno,Toshio Kudo,Izumi Kumagai,

PURPOSE: Bispecific antibodies (BsAb) have been exploited as both cancer immunodiagnostics and cancer therapeutics and show promise in clinical trials of cancer imaging and therapy. For development of BsAbs as clinical reagents, we have focused on construction of small recombinant BsAbs, called bispecific diabodies. Here, we constructed and characterized a humanized bispecific diabody. EXPERIMENTAL DESIGN: We have reported significant antitumor activity of an anti-epidermal growth factor receptor (EGFR) x anti-CD3 bispecific diabody (Ex3) in in vitro cytotoxicity assays and in vivo. We humanized the Ex3 diabody (hEx3) by grafting the complementarity-determining region and compared its biological properties with those of Ex3. We also tested its physiologic stability and ability to alter survival in xenografted mice. RESULTS: The final yield of hEx3 was 10 times that of Ex3, and refolded hEx3 and Ex3 showed identical binding profiles in EGFR-positive cell lines and EGFR-transfected Chinese hamster ovary cells. hEx3 showed dose-dependent cytotoxicity to EGFR-positive cell lines, which could be specifically inhibited by parental monoclonal antibody IgGs against EGFR or CD3 antigens. The heterodimeric structure was retained in PBS for 6 months, and growth inhibition was maintained after incubation under physiologic conditions. Coadministration of hEx3 with T-LAK cells and interleukin-2 prolonged the survival of nude mice with human colon carcinoma. CONCLUSIONS: The humanized diabody hEx3 is an attractive molecule for cancer therapy and may provide important insights into the development of EGFR-based cancer-targeting reagents.

Humanization of the bispecific epidermal growth factor receptor x CD3 diabody and its efficacy as a potential clinical reagent. Publishing Authors By Initials

R Asano,Y Sone,K Makabe,K Tsumoto,H Hayashi,Y Katayose,M Unno,T Kudo,I Kumagai,

For similar xenograft model antitumor assays research abstracts see: xenograft model antitumor assays research

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Humanization of the bispecific epidermal growth factor receptor x CD3 diabody and its efficacy as a potential clinical reagent. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Clinical cancer research : an official journal of

VOLUME: 12

Page Numbers: 4036-42

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 1

MONTH: Jul

YEAR: 2006

Humanization of the bispecific epidermal growth factor receptor x CD3 diabody and its efficacy as a potential clinical reagent. Information

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LANGUAGE: eng

NlmUniqueID: 9502500

Humanization of the bispecific epidermal growth factor receptor x CD3 diabody and its efficacy as a potential clinical reagent. Keywords Mesh Terms:

KEYWORDS: Xenograft Model Antitumor Assays

MESH TERMS: immunology

Chemical & Substance for Abstract: Humanization of the bispecific epidermal growth factor receptor x CD3 diabody and its efficacy as a potential clinical reagent. Information

Substance Name: Receptor, Epidermal Growth Factor

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for Humanization of the bispecific epidermal growth factor receptor x CD3 diabody and its efficacy as a potential clinical reagent.

AFFILIATION: Department of Biomolecular Engineering, Graduate School of Engineering, Tohoku University, Sendai, Japan.

Country: United States

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MEDLINETA: Clin Cancer Res

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