دورية أكاديمية
Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherapy in mice
| العنوان: | Bispecific antibodies targeting tumor-associated antigens and neutralizing complement regulators increase the efficacy of antibody-based immunotherapy in mice |
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| المؤلفون: | Macor, P., Secco, E., Mezzaroba, N., Zorzet, S., Durigutto, P., Gaiotto, T., De Maso, L., Biffi, S., Garrovo, C., Capolla, S., Gattei, V., Marzari, R., Tedesco, F., Sblattero, D., TRIPODO, Claudio |
| المساهمون: | Macor, P., Secco, E., Mezzaroba, N., Zorzet, S., Durigutto, P., Gaiotto, T., De Maso, L., Biffi, S., Garrovo, C., Capolla, S., Tripodo, C., Gattei, V., Marzari, R., Tedesco, F., Sblattero, D. |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2015 |
| المجموعة: | IRIS Università degli Studi di Palermo |
| مصطلحات موضوعية: | Animal, Antibodie, Antibodies, Bispecific, Antibody-Dependent Cell Cytotoxicity, Antigens, CD20, CD55, CD59, Burkitt Lymphoma, Cell Separation, Cloning, Molecular, Complement System Protein, Disease Models, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Human, Immunotherapy, Killer Cells, Natural, Macrophage, Mice, SCID, Microscopy, Fluorescence, Hematology, Cancer Research, Anesthesiology and Pain Medicine |
| الوصف: | The efficacy of antibody-based immunotherapy is due to the activation of apoptosis, the engagement of antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity (CDC). We developed a novel strategy to enhance CDC using bispecific antibodies (bsAbs) that neutralize the C-regulators CD55 and CD59 to enhance C-mediated functions. Two bsAbs (MB20/55 and MB20/59) were designed to recognize CD20 on one side. The other side neutralizes CD55 or CD59. Analysis of CDC revealed that bsAbs could kill 4-25 times more cells than anti-CD20 recombinant antibody in cell lines or cells isolated from patients with chronic lymphocytic leukemia. The pharmacokinetics of the bsAbs was evaluated in a human-SCID model of Burkitt lymphoma. The distribution profile of bsAbs mimics the data obtained by studying the pharmacokinetics of anti-CD20 antibodies, showing a peak in the tumor mass 3-4 days after injection. The treatment with bsAbs completely prevented the development of human/SCID lymphoma. The tumor growth was blocked by the activation of the C cascade and by the recruitment of macrophages, polymorphonuclear and natural killer cells. This strategy can easily be applied to the other anti-tumor C-fixing antibodies currently used in the clinic or tested in preclinical studies using the same vector with the appropriate modifications. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/24903480; info:eu-repo/semantics/altIdentifier/wos/WOS:000349445000017; volume:29; issue:2; firstpage:406; lastpage:414; numberofpages:9; journal:LEUKEMIA; http://hdl.handle.net/10447/203496Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84927171007; http://www.nature.com/leu/index.htmlTest |
| DOI: | 10.1038/leu.2014.185 |
| الإتاحة: | https://doi.org/10.1038/leu.2014.185Test http://hdl.handle.net/10447/203496Test http://www.nature.com/leu/index.htmlTest |
| حقوق: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.BC8D728F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/leu.2014.185 |
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