Construction and in vivo evaluation of an anti- PSA x anti-CD3 bispecific antibody for the immunotherapy of prostate cancer.
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.[1]References
- Construction and in vivo evaluation of an anti-PSA x anti-CD3 bispecific antibody for the immunotherapy of prostate cancer. Katzenwadel, A., Schleer, H., Gierschner, D., Wetterauer, U., Elsässer-Beile, U. Anticancer Res. (2000) [Pubmed]
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