Titre du document / Document title

Intracellular uptake and catabolism of anti-IgM antibodies and bi-specific antibody-targeted hapten by B-lymphoma cells

Auteur(s) / Author(s)

MANETTI C. ⁽¹⁾ ; LE DOUSSAL J. M. ⁽²⁾ ; ROUVIER E. ⁽¹⁾ ; GRUAZ-GUYON A. ; BARBET J. ⁽¹⁾ ;

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

⁽¹⁾ IMMUNOTECH SA, 13276 Marseille, FRANCE
⁽²⁾ INSERM Fac. médecine Saint-Antoine, U113, Paris, FRANCE

Résumé / Abstract

The efficiency of radioimmunotherapy with iodine-labelled antibodies is often limited by intracellular internalisation and catabolism after initial binding to the cellular targets. We have developed a technique called affinity enhancement system (AES) which uses bi-specific antibodies to target radiolabelled bivalent haptens to cells. This targeting method has been applied successfully to tumour imaging in colorectal cancer patients and is now considered for therapy. We have investigated the potential of this technique to target iodine radioisotopes by comparing it to targeting with covalently iodine-labelled antibodies in a rapidly internalising antigenic system, the surface IgM of a B-lymphoma cell line. A 5-fold increase in the intracellular retention time of activity as compared to ¹²⁵I-labelled F(ab')₂ or IgG was observed. The radiolabelled hapten did not undergo any catabolism after internalisation. Resistance to cellular proteases and failure of recognition of the hapten by amino acid transporter systems may be potential explanations for these observations. This should make noncovalent targeting, particularly the AES, a method of choice to target modulating antigens for the therapy of malignant hemopathies.

Revue / Journal Title

International journal of cancer   ISSN 0020-7136   CODEN IJCNAW 

Source / Source

1995, vol. 63, n^o2, pp. 250-256 (31 ref.)

Langue / Language

Anglais

Editeur / Publisher

Wiley-Liss, New York, NY, ETATS-UNIS  (1966) (Revue)

Mots-clés anglais / English Keywords

Lymphoma ; B-Lymphocyte ; Established cell line ; Human ; In vitro ; IgM ; Plasma membrane ; Hapten ; Radiolabelling ; Endocytosis ; Internalization ; Catabolism ; Immunoradiotherapy ; Bispecific antibody ; Malignant hemopathy ; Lymphoproliferative syndrome ; Non Hodgkin lymphoma ;

Mots-clés français / French Keywords

Lymphome ; Lymphocyte B ; Lignée cellulaire établie ; Homme ; In vitro ; IgM ; Membrane plasmique ; Haptène ; Marquage radioisotopique ; Endocytose ; Internalisation ; Catabolisme ; Immunoradiothérapie ; Lignée Ramos ; Complexe non covalent ; Anticorps bispécifique ; Hémopathie maligne ; Lymphoprolifératif syndrome ; Lymphome non hodgkinien ;

Mots-clés espagnols / Spanish Keywords

Linfoma ; Linfocito B ; Línea celular establecida ; Hombre ; In vitro ; IgM ; Membrana plasmática ; Hapteno ; Marcación radioisotópica ; Endocitosis ; Internalización ; Catabolismo ; Inmunoradioterapia ; Hemopatía maligna ; Linfoproliferativo síndrome ; Linfoma no Hodgkin ;

Localisation / Location

INIST-CNRS, Cote INIST : 13027, 35400005850087.0170