PMID: 8595159Feb 1, 1996Paper

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

British Journal of Cancer
E KievitEpie Boven

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 deli...Continue Reading

Citations

Jan 11, 2013·Cancer Control : Journal of the Moffitt Cancer Center·Michael B TomblynPaul E Wallner
Apr 10, 1997·International Journal of Cancer. Journal International Du Cancer·E KievitE Boven
Apr 13, 2004·Journal of Immunotherapy·Joseph P ConnorPaul Sondel
May 7, 2002·International Journal of Cancer. Journal International Du Cancer·Iris VerelGuus A M S van Dongen
Jul 9, 1999·Journal of Molecular Recognition : JMR·S V Evans, C Roger MacKenzie
May 5, 2009·Cancer Biotherapy & Radiopharmaceuticals·Stephen I Rudnick, Gregory P Adams
Dec 1, 2004·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Johann S de BonoAlbert F LoBuglio
Aug 29, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Huang YangZhengwei Mao
Jun 11, 2008·Advanced Drug Delivery Reviews·Greg M ThurberK Dane Wittrup

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