Neutralization of complement regulatory proteins augments lysis of breast carcinoma cells targeted with rhumAb anti-HER2

Katrin Jurianz, Sabine Maslak, Helena Garcia-Schüler, Zvi Fishelson, Michael Kirschfink

Research output: Contribution to journalArticlepeer-review

Abstract

The capacity of recombinant human monoclonal anti-p185(HER2) IgG (rhumAb anti-HER2) to activate human complement was investigated. Complement activation by rhumAb anti-HER2 on various human breast carcinoma cell lines resulted in deposition of complement proteins on these cells. Complement activation was also observed in a solid-phase binding assay, in which purified p185(HER2) was immobilized onto a microtiter plate. rhumAb anti-HER2 induced some complement-mediated tumor cell lysis by rabbit complement, but not by human complement. Analysis of membrane complement regulatory proteins (mCRP) on breast carcinoma cells revealed a heterogenous expression of CD46, CD55 and CD59. After blocking the mCRP activity with specific antibodies, rhumAb anti-HER2 induced about 15% lysis of p185(HER2)-expressing tumor cells. Tumor cell sensitization with rabbit polyclonal anti-tumor antiserum following mCRP neutralization, augmented cell lysis from 10 to 80%. Expression of mCRP was upregulated by treatment with PMA, and correlated with increased protection of the tumor cells from complement lysis. These results suggest that humanized antibodies like rhumAb anti-HER2 promote complement activation leading to tumor cell phagocytosis and cell-mediated cytotoxicity. They further demonstrate that a successful tumor immunotherapeutical approach, based on antibody and complement treatment, requires mCRP neutralization.

Original languageEnglish
Pages (from-to)209-218
Number of pages10
JournalImmunopharmacology
Volume42
Issue number1-3
DOIs
StatePublished - May 1999

Keywords

  • Breast carcinoma
  • Complement resistance
  • HER2
  • Humanized antibody
  • Membrane regulatory proteins

Fingerprint

Dive into the research topics of 'Neutralization of complement regulatory proteins augments lysis of breast carcinoma cells targeted with rhumAb anti-HER2'. Together they form a unique fingerprint.

Cite this