In vivo targeting of human neutralizing antibodies against CD55 and CD59 to lymphoma cells increases the antitumor activity of rituximab

Paolo Macor, Claudio Tripodo, Sonia Zorzet, Erich Piovan, Fleur Bossi, Roberto Marzari, Alberto Amadori, Francesco Tedesco

Research output: Contribution to journalArticle

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Abstract

An in vivo model of human CD20+ B-lymphoma was established in severe combined immunodeficiency mice to test the ability of human neutralizing miniantibodies to CD55 and CD59 (MB55 and MB59) to enhance the therapeutic effect of rituximab. The miniantibodies contained single-chain fragment variables and the hinge-CH2-CH3 domains of human IgG 1. LCL2 cells were selected for the in vivo study among six B-lymphoma cell lines for their high susceptibility to rituximab-dependent complement-mediated killing enhanced by MB55 and MB59. The cells injected i.p. primarily colonized the liver and spleen, leading to the death of the animals within 30 to 40 days. Thirty percent of mice receiving biotin-labeled rituximab (25 μg) i.p. on days 4 and 11 after cell injection survived to 120 days. Administration of biotin-labeled rituximab, followed by avidin (40 μg) and biotin-labeled MB55-MB59 (100 μg) at 4-h intervals after each injection resulted in the survival of 70% of mice. Surprisingly, 40% of mice survived after the sole injection of avidin and biotin-labeled MB55-MB59, an observation consistent with the in vitro data showing that the miniantibodies induced killing of ∼25% cells through antibody-dependent cell cytotoxicity. In conclusion, MB55 and MB59 targe ted to tumor cells represent a valuable tool to enhance the therapeutic effect of rituximab and other complement-fixing antitumor antibodies.

Original languageEnglish
Pages (from-to)10556-10563
Number of pages8
JournalCancer Research
Volume67
Issue number21
DOIs
Publication statusPublished - Nov 1 2007

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Neutralizing Antibodies
Lymphoma
Biotin
Avidin
Therapeutic Uses
Injections
Antibody-Dependent Cell Cytotoxicity
Severe Combined Immunodeficiency
Single-Chain Antibodies
Spleen
Immunoglobulin G
Observation
Rituximab
Cell Line
Survival
Antibodies
Liver
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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In vivo targeting of human neutralizing antibodies against CD55 and CD59 to lymphoma cells increases the antitumor activity of rituximab. / Macor, Paolo; Tripodo, Claudio; Zorzet, Sonia; Piovan, Erich; Bossi, Fleur; Marzari, Roberto; Amadori, Alberto; Tedesco, Francesco.

In: Cancer Research, Vol. 67, No. 21, 01.11.2007, p. 10556-10563.

Research output: Contribution to journalArticle

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