The role of monoclonal antibody affinity in tumor immunotherapy evaluated in in vivo models for minimal residual disease.

Abstract

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.

• Authors: M P Velders, C M van Rhijn, I M Cornelissen, G N van Muijen, I H Briaire, M Dohlsten, G J Fleuren, S O Warnaar, S V Litvinov
• Journal: Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy (J Immunother Emphasis Tumor Immunol) Vol. 19 Issue 4 Pg. 245-56 (Jul 1996) ISSN: 1067-5582 [Print] United States
• PMID: 8877719 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal

Topics

• Animals
• Antibodies, Monoclonal (therapeutic use)
• Antibody Affinity (immunology)
• Disease Models, Animal
• Flow Cytometry
• Immunotherapy (methods)
• Lung Neoplasms (secondary, therapy)
• Male
• Melanoma, Experimental (genetics, therapy)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Nude
• Neoplasm, Residual (therapy)
• Skin Neoplasms (therapy)
• Transfection (genetics)