chFRP5-ZZ-PE38, a large IgG-toxin immunoconjugate outperforms the corresponding smaller FRP5(Fv)-ETA immunotoxin in eradicating ErbB2-expressing tumor xenografts

Yariv Mazor, Roy Noy, Winfried S. Wels, Itai Benhar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

As therapeutics, antibodies can be used "un-armed" or as immunoconjugates to direct cytotoxic moieties to tumor cells. Immunoconjugates are made by attaching chemotherapy drugs, radioisotopes or toxins to the antibody. Small recombinant antibody fragments fused to cytotoxic moieties, termed recombinant immunotoxins are also being developed as an additional approach for a targeted cancer therapy. Key parameters in determining the therapeutic potential of such targeted therapies are target specificity, affinity, stability and size. With regard to treating solid tumors, tumor penetration (which is inversely proportional to size) is currently regarded as the prime factor for efficacy, while parameters such as binding affinity and residence time in the body are thought to contribute to a lesser extent. When comparing recombinant immunotoxins and antibody-toxin immunoconjugates that target ErbB2/HER2, here we found that a bivalent antibody-toxin immunoconjugate (200 kDa) was superior to the corresponding recombinant monovalent immunotoxin (69 kDa) in killing ErbB2-expressing tumor cells in culture and as xenografts in nude mice, suggesting that higher avidity and longer residence time may outweigh tumor penetration. Our study suggests that the re-valuation of currently neglected, large IgG-effector molecule conjugates for anti-cancer therapy may be justified.

Original languageEnglish
Pages (from-to)124-135
Number of pages12
JournalCancer Letters
Volume257
Issue number1
DOIs
StatePublished - 8 Nov 2007

Keywords

  • ErbB-2/HER2
  • ZZ-PE38
  • chFRP5-ZZ-PE38 immunoconjugate
  • scFv(FRP5)-ETA immunotoxin

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