Neutralization of complement regulatory proteins augments lysis of breast carcinoma cells targeted with rhumAb anti-HER2
The capacity of recombinant human monoclonal anti-p185HER2 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...
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| Main Authors: | , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
17 June 1999
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| In: |
Immunopharmacology
Year: 1999, Volume: 42, Issue: 1-3, Pages: 209-218 |
| ISSN: | 1879-047X |
| DOI: | 10.1016/s0162-3109(99)00006-5 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/s0162-3109(99)00006-5
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| Author Notes: | K. Jurianz, S. Maslak, H. Garcia-Schüler, Z. Fishelson, M. Kirschfink |
| Summary: | The capacity of recombinant human monoclonal anti-p185HER2 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 p185HER2 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 p185HER2-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. |
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| Item Description: | Gesehen am 17.02.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1879-047X |
| DOI: | 10.1016/s0162-3109(99)00006-5 |