Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising natural anticancer therapeutic agent because through its death receptors, TRAIL-R1 and TRAIL-R2, it induces apoptosis in many transformed tumor cells, but not in the majority of normal cells. Hence, agonistic compounds directed against TRAIL death receptors have the potential of being excellent cancer therapeutic agents, with minimal cytotoxicity in normal tissues. Here, we report the selection and characterization of a new single-chain fragment variable (scFv) to TRAIL-R2 receptor isolated from a human phage-display library, produced as minibody (MB), and characterized for the in vitro anti-leukemic tumoricidal activity. The anti-TRAIL-R2 MB2.23 efficiently and specifically bound to membrane-associated TRAIL-R2 on different leukemic cell lines and could act as a direct agonist in vitro, initiating apoptotic signaling as well as complement-dependent cytotoxicity and antibody-dependent cell cytotoxicity, providing a rationale for further investigations of MB2.23 in anticancer therapy.

Secchiero, P., Sblattero, D., Chiaruttini, C., Melloni, E., Macor, P., Zorzet, S., et al. (2009). Selection and characterization of a novel agonistic human recombinant anti-TRAIL-R2 minibody with anti-leukemic activity. INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY, 22(1), 73-83.

Selection and characterization of a novel agonistic human recombinant anti-TRAIL-R2 minibody with anti-leukemic activity

TRIPODO, Claudio;
2009-01-01

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising natural anticancer therapeutic agent because through its death receptors, TRAIL-R1 and TRAIL-R2, it induces apoptosis in many transformed tumor cells, but not in the majority of normal cells. Hence, agonistic compounds directed against TRAIL death receptors have the potential of being excellent cancer therapeutic agents, with minimal cytotoxicity in normal tissues. Here, we report the selection and characterization of a new single-chain fragment variable (scFv) to TRAIL-R2 receptor isolated from a human phage-display library, produced as minibody (MB), and characterized for the in vitro anti-leukemic tumoricidal activity. The anti-TRAIL-R2 MB2.23 efficiently and specifically bound to membrane-associated TRAIL-R2 on different leukemic cell lines and could act as a direct agonist in vitro, initiating apoptotic signaling as well as complement-dependent cytotoxicity and antibody-dependent cell cytotoxicity, providing a rationale for further investigations of MB2.23 in anticancer therapy.
2009
Secchiero, P., Sblattero, D., Chiaruttini, C., Melloni, E., Macor, P., Zorzet, S., et al. (2009). Selection and characterization of a novel agonistic human recombinant anti-TRAIL-R2 minibody with anti-leukemic activity. INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY, 22(1), 73-83.
File in questo prodotto:
File Dimensione Formato  
Secchiero_trail_R2_FINAL.pdf

Solo gestori archvio

Dimensione 691.5 kB
Formato Adobe PDF
691.5 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/203586
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 8
social impact