| Autor: |
Velders MP; Department of Pathology, Leiden University Hospital, The Netherlands., van Rhijn CM, Cornelissen IM, van Muijen GN, Briaire IH, Dohlsten M, Fleuren GJ, Warnaar SO, Litvinov SV |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy [J Immunother Emphasis Tumor Immunol] 1996 Jul; Vol. 19 (4), pp. 245-56. |
| DOI: |
10.1097/00002371-199607000-00001 |
| Abstrakt: |
To evaluate the role of affinity in monoclonal antibody (mAb)-mediated treatment of carcinomas, we compared the antibodies 17-1A and 323/A3 that bind with different affinities overlapping epitopes on the epithelial adhesion molecule Ep-CAM. This comparison was performed in several models for minimal residual disease in mice grafted with Ep-CAM transfected B16 melanoma cells originating from C57BL/6 mice. These cells were either grafted subcutaneously or injected intravenously into nude BALB/c mice, or grafted subcutaneously in immunocompetent C57BL/6 mice. In the BALB/c subcutaneous model, significant therapeutic results (p < 0.05) compared with the control mAb were obtained with both mAbs 17-1A and 323/A3. However, when treating lung metastases in nude BALB/c mice that had developed after intravenous injection of the B16/Ep-CAM tumor cells, only the high-affinity 323/A3 mAb could significantly (p < 0.05) reduce the number of metastases that appeared. In syngeneic C57BL/6 mice grafted subcutaneously with B16/ Ep-CAM cells, a single 323/A3 or 17-1A mAb injection had no effect, in contrast to that observed for the nude BALB/c mouse model. However, multiple injections of the 323/A3 mAb significantly (p < 0.005) reduced the mean tumor volume, although they did not prevent tumor development. The results show that in vivo antibody-mediated effector cell activation and subsequent tumor cell elimination is determined by mAb affinity and target antigen density. Therefore, treatment of minimal residual disease with high-affinity mAb 323/ A3 is expected to improve the clinical results obtained with mAb 17-1A. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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