دورية أكاديمية
Construction and in vivo evaluation of an anti-PSA x anti-CD3 bispecific antibody for the immunotherapy of prostate cancer.
| العنوان: | Construction and in vivo evaluation of an anti-PSA x anti-CD3 bispecific antibody for the immunotherapy of prostate cancer. |
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| المؤلفون: | Katzenwadel A; Department of Urology, University of Freiburg, Germany., Schleer H, Gierschner D, Wetterauer U, Elsässer-Beile U |
| المصدر: | Anticancer research [Anticancer Res] 2000 May-Jun; Vol. 20 (3A), pp. 1551-5. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: International Institute of Anticancer Research Country of Publication: Greece NLM ID: 8102988 Publication Model: Print Cited Medium: Print ISSN: 0250-7005 (Print) Linking ISSN: 02507005 NLM ISO Abbreviation: Anticancer Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Attiki, Greece : International Institute of Anticancer Research Original Publication: Athens, Greece : Potamitis Press |
| مواضيع طبية MeSH: | Immunotherapy*, Antibodies, Bispecific/*therapeutic use , CD3 Complex/*immunology , Prostate-Specific Antigen/*immunology , Prostatic Neoplasms/*therapy, Animals ; Antibodies, Bispecific/adverse effects ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal/therapeutic use ; Disease Models, Animal ; Evaluation Studies as Topic ; Humans ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; Prostatic Neoplasms/immunology ; T-Lymphocytes/immunology ; Transplantation, Heterologous |
| مستخلص: | Background: Cross-linking of tumor antigens with the T-cell associated CD3 antigen can be effectively achieved by bispecific monoclonal antibodies and lead to an increase in antigen-specific cytotoxicity in T cells. Because of the high organ specificity of the prostate specific antigen (PSA), a bispecific antibody (BiAb) directed against this antigen and CD3 may be a tool for a highly specific immune therapy of prostate cancer. Methods: For generating BiAb, the quadroma technique was used. Binding properties both to CD3 and PSA were shown by flow cytometry with the CD3 expressing Jurkat cell line and fluorescein-labeled PSA. Specific tumor cell lysis was tested with the PSA expressing prostate carcinoma cell line LNCaP as target and interleukin-2 activated human peripheral blood lymphocytes as effector cells in a chromium-51-release assay. For in vivo evaluation of the BiAb, a nude mouse model was used. The mice were inoculated with LNCaP prostate carcinoma cells. Animals with growing tumors were treated with 100 micrograms BiAb and 5 x 10(6) effector cells. Results: Three stable quadromas producing anti-CD3 x anti-PSA BiAb were established. From the culture supernatant of one quadroma, BiAb was separated by affinity chromatography and tested in vitro and in vivo for its ability to target effector T lymphocytes against appropriate tumor cells. In vitro, a specific lysis of PSA expressing prostate carcinoma cells was demonstrated. In vivo, a significant reduction in tumor growth (p < 0.05) could be shown in nude mice treated with BiAb and effector cells as compared to a group treated only with effector cells and an untreated control group. Conclusion: In the present study, an anti-CD3 x anti-PSA-BiAb was demonstrated to be effective against prostate carcinoma cells in vitro and in vivo. Therefore this BiAb may be a tool for the immunotherapy of prostate cancer. |
| المشرفين على المادة: | 0 (Antibodies, Bispecific) 0 (Antibodies, Monoclonal) 0 (CD3 Complex) EC 3.4.21.77 (Prostate-Specific Antigen) |
| تواريخ الأحداث: | Date Created: 20000806 Date Completed: 20000817 Latest Revision: 20171116 |
| رمز التحديث: | 20221213 |
| PMID: | 10928069 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 0250-7005 |
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