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Titre du document / Document title

Immunotherapeutic effect of concholepas hemocyanin in the murine bladder cancer model : Evidence for conserved antitumor properties among hemocyanins

Auteur(s) / Author(s)

MOLTEDO Bruno (1) ; FAUNES Fernando (1) ; HAUSSMANN Denise (1) ; DE IOANNES Pablo (1) ; DE IOANNES Alfredo E. (1) ; PUENTE Javier (2) ; BECKER Maria Inés (1) ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

(1) Department of Research and Development, Biosonda Corp, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, CHILI
(2) Department of Biochemistry and Molecular Biology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santiago, CHILI

Résumé / Abstract

Purpose: We determined the antitumor properties of a newly available hemocyanin obtained from the Chilean gastropod Concholepas concholepas (Biosonda Corp., Santiago, Chile) in a syngeneic heterotopic mouse bladder carcinoma model. Since keyhole limpet hemocyanin (Pierce, Rockford, Illinois) is used increasingly in biomedicine as a carrier for vaccines and an immunotherapeutic agent for bladder transitional cell carcinoma, there is a growing interest in finding new substances that share its potent immunomodulatory properties. Considering that keyhole limpet hemocyanin and Concholepas concholepas hemocyanin differ significantly, it was not possible to predict a priori the antitumor properties of Concholepas concholepas hemocyanin. Materials and Methods: C3H/He mice were primed with Concholepas concholepas hemocyanin before subcutaneous implantation of mouse bladder tumor-2 cells. Treatment consisted of a subcutaneous dose of Concholepas concholepas hemocyanin (1 mg or 100 μg) at different intervals after implantation. Keyhole limpet hemocyanin and phosphate buffered saline served as positive and negative controls, respectively. In addition, experiments were designed to determine which elements of the immune response were involved in its adjuvant immunostimulatory effect. Results: Mice treated with Concholepas concholepas hemocyanin showed a significant antitumor effect, as demonstrated by decreased tumor growth and incidence, prolonged survival and lack of toxic effects. These effects were similar to those achieved with keyhole limpet hemocyanin. We found that each hemocyanin increased natural killer cell activity but the effect of Concholepas concholepas hemocyanin was stronger. Analysis of serum from treated mice showed an increased interferon-y and low interleukin-4, which correlated with antibody isotypes, confirming that hemocyanins induce a T helper type 1 cytokine profile. Conclusions: To our knowledge our results are the first demonstration of the antitumor effect of a hemocyanin other than keyhole limpet hemocyanin. They suggest that this is an ancient conserved immunogenic mechanism shared by those hemocyanins that is able to enhance T helper type 1 immunity and lead to antitumor activity. Therefore, Concholepas concholepas hemocyanin may be an alternative candidate for providing safe and effective immunotherapy for human superficial bladder cancer.

Revue / Journal Title

The Journal of urology    ISSN  0022-5347   CODEN JOURAA 

Source / Source

2006, vol. 176 (1), no6, pp. 2690-2695 [6 page(s) (article)] (20 ref.)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, New York, NY, ETATS-UNIS  (1917) (Revue)

Mots-clés anglais / English Keywords

Urinary system

;

Urinary tract disease

;

Bladder disease

;

Malignant tumor

;

Urinary system disease

;

Invertebrata

;

Mollusca

;

Vertebrata

;

Mammalia

;

Rodentia

;

Nephrology

;

Urology

;

Gastropoda

;

Treatment

;

Immunotherapy

;

Urinary bladder

;

Antineoplastic agent

;

Mouse

;

Bladder tumor

;

Animal model

;

Hemocyanin

;

Bladder cancer

;

Mots-clés français / French Keywords

Appareil urinaire

;

Voie urinaire pathologie

;

Vessie pathologie

;

Tumeur maligne

;

Appareil urinaire pathologie

;

Invertebrata

;

Mollusca

;

Vertebrata

;

Mammalia

;

Rodentia

;

Néphrologie

;

Urologie

;

Gastropoda

;

Traitement

;

Immunothérapie

;

Vessie urinaire

;

Anticancéreux

;

Souris

;

Tumeur vessie urinaire

;

Modèle animal

;

Hémocyanine

;

Cancer vessie

;

Mots-clés espagnols / Spanish Keywords

Aparato urinario

;

Vía urinaria patología

;

Vejiga patología

;

Tumor maligno

;

Aparato urinario patología

;

Invertebrata

;

Mollusca

;

Vertebrata

;

Mammalia

;

Rodentia

;

Nefrología

;

Urología

;

Gastropoda

;

Tratamiento

;

Inmunoterapia

;

Vejiga

;

Anticanceroso

;

Ratón

;

Tumor vejiga

;

Modelo animal

;

Hemocianina

;

Cáncer de la vejiga

;

Mots-clés d'auteur / Author Keywords

bladder

;

bladder neoplasms

;

hemocyanin

;

immunotherapy

;

Gastropoda

;

Localisation / Location

INIST-CNRS, Cote INIST : 2081, 35400015900690.0640

Nº notice refdoc (ud4) : 18281377



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