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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| Hauptverfasser: | , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
17 June 1999
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| In: |
Immunopharmacology
Year: 1999, Jahrgang: 42, Heft: 1-3, Pages: 209-218 |
| ISSN: | 1879-047X |
| DOI: | 10.1016/s0162-3109(99)00006-5 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/s0162-3109(99)00006-5
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| Verfasserangaben: | K. Jurianz, S. Maslak, H. Garcia-Schüler, Z. Fishelson, M. Kirschfink |
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| 245 | 1 | 0 | |a Neutralization of complement regulatory proteins augments lysis of breast carcinoma cells targeted with rhumAb anti-HER2 |c K. Jurianz, S. Maslak, H. Garcia-Schüler, Z. Fishelson, M. Kirschfink |
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| 520 | |a 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. | ||
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Antibodies, Monoclonal | |
| 650 | 4 | |a Antibody Specificity | |
| 650 | 4 | |a Breast Neoplasms | |
| 650 | 4 | |a Carcinoma | |
| 650 | 4 | |a Complement Activation | |
| 650 | 4 | |a Complement System Proteins | |
| 650 | 4 | |a Flow Cytometry | |
| 650 | 4 | |a Humans | |
| 650 | 4 | |a Immunization, Passive | |
| 650 | 4 | |a Immunoglobulin G | |
| 650 | 4 | |a Neoplasm Proteins | |
| 650 | 4 | |a Rabbits | |
| 650 | 4 | |a Receptor, ErbB-2 | |
| 650 | 4 | |a Recombinant Proteins | |
| 650 | 4 | |a Tumor Cells, Cultured | |
| 700 | 1 | |a Maslak, Sabine |e VerfasserIn |4 aut | |
| 700 | 1 | |a Garcia-Huttenlocher, Helena Isabel |d 1974- |e VerfasserIn |0 (DE-588)130881643 |0 (DE-627)507233832 |0 (DE-576)251498581 |4 aut | |
| 700 | 1 | |a Fishelson, Zvi |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kirschfink, Michael |e VerfasserIn |0 (DE-588)120927152 |0 (DE-627)080974457 |0 (DE-576)292452411 |4 aut | |
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