Generation, immunologic characterization and antitumor effects of human monoclonal antibodies for carcinoembryonic antigen

Imakiire, Takanori; Shibaguchi, Hirotomo; Abe, Hironori; Yamauchi, Yasushi; Ueno, Aruto; Hirose, Yuki; Yamada, Hiromi; Yamashita, Yuichi; Shirakusa, Takayuki; Kuroki, Masahide

doi:10.1002/ijc.11608

Cited by 29 publications

(22 citation statements)

References 31 publications

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“…In the present study, we used the C2-45 clone (IgG4, n) as the fully human anti-CEA mAb. Preparation of the antibody has been described previously in detail (23). Mouse mAb clones F33-104 (IgG1, n), F33-60 (IgG2a, n), F82-81 (IgG2b, n), and F11-12 (IgG3, n) against human CEA (31) and mouse-human chimeric mAb ChF11-39 (IgG1; ref.…”

Section: Methodsmentioning

confidence: 99%

Carcinoembryonic Antigen–Targeted Selective Gene Therapy for Gastric Cancer through FZ33 Fiber-Modified Adenovirus Vectors

Tanaka

Huang

Hirai

et al. 2006

Clinical Cancer Research

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Purpose: A major problem when using the adenoviral vectors for gene therapy applications is thought to be related to low transduction efficiency in cancer cells or to side effects in normal cells. There is an urgent requirement to improve the specificity of gene delivery in the context of cancer gene therapy. Experimental Design: We constructed a genetically modified adenovirus incorporating an IgG Fc-binding motif from the Staphylococcus protein A, Z33, within the HI loop (Adv-FZ33). A remarkable degree of targeted gene delivery to gastric cancer cells was obtained with Adv-FZ33 with the fully human anti^carcinoembryonic antigen (CEA) monoclonal antibody, C2-45. Results: In vitro LacZ or EGFP gene expression afterAdv-FZ33 infection via C2-45 was 20 times higher than control monoclonal antibody in MKN-45 at 1,000 viral particles/cell. We generated Ax3CAUP-FZ33 (UP-FZ33), which is an Adv-FZ33 derivative vector expressing a therapeutic gene (i.e., Escherichia coli uracil phosphoribosyltransferase), which converts 5-fluorouracil (5-FU) directly to 5-fluoro-UMP. UP-FZ33 with C2-45 enhanced the cytotoxicity of 5-FU by 10.5-fold in terms of IC 50 against MKN-45 compared with control IgG4. In a nude mouse peritoneal dissemination model, tumor growth in mice treated with UP-FZ33/C2-45/5-FU was significantly suppressed, and tumor volumes were less than one-fourth of those of the control IgG4 group (P < 0.05). The median survival time of the UP-FZ33/C2-45/5-FU group was significantly longer than those treated with PBS or 5-FU only (P < 0.01).Conclusions: These data suggest that CEA-targeted FZ33 mutant adenovirus-mediated gene delivery offers a strong and selective therapeutic modality against CEA-producing cancers.

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Section: Methodsmentioning

confidence: 99%

Carcinoembryonic Antigen–Targeted Selective Gene Therapy for Gastric Cancer through FZ33 Fiber-Modified Adenovirus Vectors

Tanaka

Huang

Hirai

et al. 2006

Clinical Cancer Research

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“…Ils ont ainsi permis de dériver un certain nombre d'anticorps de forte affinité et d'intérêt commercial important, reconnaissant aussi bien des petites molécules [15], des protéines spécifiques de pathogènes [16,17], des polysaccharides [18], des protéines humaines solubles et des cytokines comme l'interleukine-15 [19][20][21] ou membranaires comme l'antigène spécifique de prostate PSMA, le CD20, le CD30 ou le récepteur à l'EGF (epidermal growth factor) [22][23][24] et des antigènes associés à des tumeurs comme l'antigène carcinoembryonnaire [25]. Les premiers résultats à propos de tous ces Acm semblent très encourageants quant à leur faible immunogé-nicité chez l'homme (➜).…”

Section: Exemples D'anticorps Thérapeutiques Humanisésunclassified

Transgenèse animale et humanisation des anticorps

2009

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“…The fully human monoclonal anti-CEA Abs, C2-24, C2-45, C2-74 and C2-78, were generated using KMmouse immunized with CEA as described previously [30]. The murine anti-CEACAM6 Abs (9A6 or YTH71.3, anti-CEACAM6 or anti-CEACAM1/3/6 Ab, respectively) and the control human IgG were purchased from Santa Cruz Biotechnology, Inc. (Santa Cruz, Calif., USA) and from Baxter International Inc. (Deerfield, Ill., USA), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…We previously generated fully human monoclonal Abs specific to CEA using KMmouse™ immunized with CEA and demonstrated the antitumor effect of C2-74 on MKN-45 cells, a CEA-positive human colon cell line, in vitro and in vivo [30]. As mentioned above, the anticancer effect of C2-74 has three possible mechanisms: ADCC, CDC activity and the prevention of CEA interaction with ECM and/or intercellular adhesion molecules, resulting in anoikis.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of the Antitumor Effect on Combination Therapy of an Anticancer Drug and Its Antibody against Carcinoembryonic Antigen

Shibaguchi¹,

Tsuru²,

Kuroki

2012

Chemotherapy

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Background: Carcinoembryonic antigen (CEA) is frequently overexpressed in various types of human cancers and is associated with cell adhesion. There are three possible mechanisms of cancer therapy that employ anti-CEA antibody (Ab): Ab-dependent cell-mediated cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC) or the prevention of CEA interaction with the extracellular matrix and/or intercellular adhesion molecules resulting in anoikis. In this study, the effect of C2-74, a human anti-CEA monoclonal Ab was evaluated. Methods: ADCC, CDC and anoikis assays in combination with C2-74 and an anticancer drug (5-fluorouracil or cisplatin) were investigated using tumor cell lines (MKN-45, MKN-74 and KATO III). In the anoikis assay, other human anti-CEA Abs and mouse anti-CEA-related cell adhesion molecule 6 Abs were also investigated using HLC-1 cells. Results: Additive cytotoxicity was observed when the anticancer drug and C2-74 on tumor cells were combined in the CDC assays, whereas in the anoikis assay, no such additive effect was observed. Anti-CEA-related cell adhesion molecule 6 Abs, but not anti-CEA Abs, accelerated anoikis in HLC-1 cells. Conclusion: A mechanism for the additive antitumor effect when an anticancer drug and C2-74 are combined is indicated mainly by CDC activity but is irrelevant to anoikis in tumor cells.

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Generation, immunologic characterization and antitumor effects of human monoclonal antibodies for carcinoembryonic antigen

Abstract: We generated fully human mAbs (HmAbs) to carcinoembryonic antigen (CEA) using the KM mouse, which carries a human chromosome 14 fragment containing the entire Ig H chain loci and human L chain segments in the mouse genome. Forty-six hybridoma clones producing HmAbs to

Cited by 29 publications

References 31 publications

Carcinoembryonic Antigen–Targeted Selective Gene Therapy for Gastric Cancer through FZ33 Fiber-Modified Adenovirus Vectors

Carcinoembryonic Antigen–Targeted Selective Gene Therapy for Gastric Cancer through FZ33 Fiber-Modified Adenovirus Vectors

Transgenèse animale et humanisation des anticorps

Enhancement of the Antitumor Effect on Combination Therapy of an Anticancer Drug and Its Antibody against Carcinoembryonic Antigen

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