Efficient killing of CD22+ tumor cells by a humanized diabody-RNase fusion protein.
Biochem Biophys Res Commun
; 331(2): 595-602, 2005 Jun 03.
Article
en En
| MEDLINE
| ID: mdl-15850802
ABSTRACT
We report on the generation of a dimeric immunoenzyme capable of simultaneously delivering two ribonuclease (RNase) effector domains on one molecule to CD22(+) tumor cells. As targeting moiety a diabody derived from the previously humanized scFv SGIII with grafted specificity of the murine anti-CD22 mAb RFB4 was constructed. Further engineering the interface of this construct (V(L)36(Leu-->Tyr)) resulted in a highly robust bivalent molecule that retained the same high affinity as the murine mAb RFB4 (K(D)=0.2 nM). A dimeric immunoenzyme comprising this diabody and Rana pipiens liver ribonuclease I (rapLRI) was generated, expressed as soluble protein in bacteria, and purified to homogeneity. The dimeric fusion protein killed several CD22(+) tumor cell lines with high efficacy (IC(50)=3-20 nM) and exhibited 9- to 48-fold stronger cytotoxicity than a monovalent rapLRI-scFv counterpart. Our results demonstrate that engineering of dimeric antibody-ribonuclease fusion proteins can markedly enhance their biological efficacy.
Buscar en Google
Banco de datos:
MEDLINE
Asunto principal:
Ribonucleasas
/
Proteínas Recombinantes de Fusión
/
Antígenos de Diferenciación de Linfocitos B
/
Antígenos CD
/
Moléculas de Adhesión Celular
/
Citotoxicidad Inmunológica
/
Lectinas
/
Anticuerpos Monoclonales
/
Neoplasias
Tipo de estudio:
Diagnostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2005
Tipo del documento:
Article
País de afiliación:
Alemania