Comparison of monoclonal antibodies 17-1A and 323/A3: the influence of the affinity on tumour uptake and efficacy of radioimmunotherapy in human ovarian cancer xenografts.

Abstract

The low-affinity monoclonal antibody (MAb) chimeric 17-1A(c-17-1A) and the high-affinity MAb mouse 323/A3 (m-323/A3) were used to study the effect of the MAb affinity on the tumour uptake and efficacy of radioimmunotherapy in nude mice bearing subcutaneously the human ovarian cancer xenografts FMa, OVCAR-3 and Ov.Pe. Both MAbs are directed against the same pancarcinoma glycoprotein. In vitro, the number of binding sites on tumour cells at 4 degrees C was similar for both MAbs, but m-323/A3 had an approximately 5-fold higher affinity (1.3-3.0x10(9) M-1) than c-17-1A (3.0-5.4x10(8) M-1). This difference in affinity was more extreme at 37 degrees C, when no binding of c-17-1A could be observed. MAb m-323/A3 completely blocked binding of c-17-1A to tumour cells, whereas the reverse was not observed. Immunohistochemistry showed a similar but more intense staining pattern of m-323/A3 in human ovarian cancer xenografts than of c-17-1A. In vivo, the blood clearance in non-tumour-bearing nude mice was similar for both MAbs with terminal half-lives of 71.4 h for m-323/A3 and 62.7 h for c-17-1A. MAb m-323/A3 targeted better to tumour tissue, but was more heterogeneously distributed than c-17-1A. The cumulative absorbed radiation dose delivered by m-323/A3 to tumour tissue was 2.5- to 4.7-fold higher than that delivered by c-17-1A. When mice were treated with equivalent radiation doses of 131(I)m-323/A3 and 131(I)c-17-1A, based on a correction for the immunoreactivity of the radiolabelled MAbs, m-323/A3 induced a better growth inhibition in two of the three xenografts. When the radiation doses were adjusted to obtain a similar amount of radiation in the tumour c-17-1A was more effective in tumour growth inhibition in all three xenografts.

• Authors: E Kievit, H M Pinedo, H M Schlüper, H J Haisma, E Boven
• Journal: British journal of cancer (Br J Cancer) Vol. 73 Issue 4 Pg. 457-64 (Feb 1996) ISSN: 0007-0920 [Print] England
• PMID: 8595159 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Immunoglobulin G
• Iodine Radioisotopes
• Recombinant Fusion Proteins

Topics

• Animals
• Antibodies, Monoclonal (immunology, metabolism, therapeutic use)
• Antibody Affinity
• Binding, Competitive
• Biological Transport
• Cell Line
• Female
• Humans
• Immunoglobulin G (immunology, metabolism, therapeutic use)
• Iodine Radioisotopes (pharmacokinetics, therapeutic use)
• Mice
• Mice, Nude
• Multivariate Analysis
• Neoplasm Transplantation
• Ovarian Neoplasms (immunology, metabolism, radiotherapy)
• Recombinant Fusion Proteins (pharmacokinetics)
• Transplantation, Heterologous
• Tumor Cells, Cultured