RGD Reference Report - Potent in vitro and in vivo antitumor activity of interleukin-4-conjugated Pseudomonas exotoxin against human biliary tract carcinoma. - Rat Genome Database

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Potent in vitro and in vivo antitumor activity of interleukin-4-conjugated Pseudomonas exotoxin against human biliary tract carcinoma.

Authors: Ishige, K  Shoda, J  Kawamoto, T  Matsuda, S  Ueda, T  Hyodo, I  Ohkohchi, N  Puri, RK  Kawakami, K 
Citation: Ishige K, etal., Int J Cancer. 2008 Dec 15;123(12):2915-22.
RGD ID: 2317263
Pubmed: PMID:18798553   (View Abstract at PubMed)
DOI: DOI:10.1002/ijc.23865   (Journal Full-text)

Targeting cytotoxins or immunotoxins to tumor cell surface receptors represents a new approach for the treatment of cancers. We tested the antitumor activity of a cytotoxin (IL-4-PE) composed of an interleukin-4 (IL-4) targeting moiety and a truncated form of Pseudomonas exotoxin A against human biliary tract carcinoma (BTC). Immunohistochemical analysis showed that cultured BTC cell lines and cancerous epithelia in BTC tissue (e.g., gallbladder carcinoma, extrahepatic cholangiocarcinoma, and intrahepatic cholangiocarcinoma) expressed receptors for IL-4 in situ at high densities. However, normal epithelial cells in gallbladder and bile duct tissues did not express these IL-4 receptors. Eight BTC cell lines expressed IL-4R on the cell surface as determined by radiolabeled ligand binding assays. When these cells were treated with IL-4-PE, significant cytotoxicity was observed as determined by the inhibition of protein synthesis. The concentration of agent causing 50% inhibition of protein synthesis (IC(50)) was found to be less than 10 ng/mL in 4 of the 8 BTC cell lines studied. The antitumor activity of IL-4-PE was assessed for human BTC cells implanted subcutaneously in immunodeficient mice. By intratumoral injection of IL-4-PE, complete disappearance of the established tumors was observed in 40% of animals. Intraperitoneal administration of IL-4-PE at tolerated doses to animals with peritoneally disseminated BTC exhibited significantly prolonged survival compared to untreated animals (>14 weeks vs. 5 weeks in treated and untreated mice, respectively). These results indicate that IL-4 receptor-targeted cytotoxin is a potent agent that may provide a new therapeutic option for BTC.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
biliary tract benign neoplasm  IMP 2317263 RGD 
biliary tract benign neoplasm  ISOIL4 (Homo sapiens)2317263; 2317263 RGD 
cholangiocarcinoma  IEP 2317263mRNA:increased expression:bile ductRGD 
cholangiocarcinoma  ISOIL4R (Homo sapiens)2317263; 2317263mRNA:increased expression:bile ductRGD 
Gallbladder Neoplasms  IEP 2317263mRNA:increased expression:gallbladderRGD 
Gallbladder Neoplasms  ISOIL4R (Homo sapiens)2317263; 2317263mRNA:increased expression:gallbladderRGD 

Objects Annotated

Genes (Rattus norvegicus)
Il4  (interleukin 4)
Il4r  (interleukin 4 receptor)

Genes (Mus musculus)
Il4  (interleukin 4)
Il4ra  (interleukin 4 receptor, alpha)

Genes (Homo sapiens)
IL4  (interleukin 4)
IL4R  (interleukin 4 receptor)


Additional Information