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

E. Kievit, H. M. Pinedo, H. M M Schlüper, H. J. Haisma, E. Boven

Research output: Contribution to journalArticlepeer-review

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°C was similar for both MAbs, but m-323/A3 had an approximately 5-fold higher affinity (1.3-3.0 x 109 M-1) than c-17-1A (3.0-5.4 x 108 M-1). This difference in affinity was more extreme at 37°C, when no binding of c-17-1A could be observed. MAb m-323/A3 completely blocked the 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 [131I]m-323/A3 and [131I]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.

Original languageEnglish (US)
Pages (from-to)457-464
Number of pages8
JournalBritish Journal of Cancer
Volume73
Issue number4
StatePublished - 1996
Externally publishedYes

Keywords

  • Biodistribution
  • C-17-1A
  • M-323/A3
  • MAb affinity
  • Radioimmunotherapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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