Effect of the extent of chelate substitution on the immunoreactivity and biodistribution of 2IT-BAT-Lym-1 immunoconjugates

D. L. Kukis, Gerald L Denardo, S. J. DeNardo, G. R. Mirick, L. A. Miers, D. P. Greiner, C. F. Meares

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

Trial therapy for lyphoma with the radiolabeled chelate-antibody conjugate 67Cu-2IT-BAT-Lym-1 has been promising. It is desirable to deliver therapeutic doses of radiometal using a minimum amount of 2IT-BAT-Lym-1 to minimize the risks of adverse patient reaction and antigenic response to antibody. This is readily accomplished by increasing the number of metal- binding sites (i.e., chelating agents) conjugated per antibody, but the ability of the antibody to bind antigen and target tumor cells in vivo must not be impaired by the conjugation reaction. To determine the maximum chelator:antibody ratio (c/a) of 2IT-BAT-Lym-1 at which functional integrity is preserved, immunoconjugates with a c/a of 1.3-23 were prepared and examined by radioimmunoassay and competitive antigen binding versus lightly iodinated Lym-1. The biodistribution in rumored mice of conjugates with c/a of 2.1, 4.3, 8.4, and 11.4 also was examined. Conjugates with c/a up to 5 exhibited no loss of immunoreactivity, and conjugates with c/a up to 11 retained 75% or greater immunoreactivity relative to unmodified Lym-1. All conjugates examined competed less effectively than did unmodified Lym-1 for antigen binding, but the effect at c/a 5 was slight. Tumor uptake declined with increasing c/a, but the effect was insignificant at c/a 2.1 and 4.3. Conjugates of c/a 4-5 were found to be optimal for the preparation of radioimmunoconjugate of high specific activity with minimal, if any, loss of functional integrity.

Original languageEnglish (US)
Pages (from-to)878-884
Number of pages7
JournalCancer Research
Volume55
Issue number4
StatePublished - 1995

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Immunoconjugates
Chelating Agents
Antibodies
Antigens
Competitive Binding
Neoplasm Antigens
Antibody Formation
Radioimmunoassay

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kukis, D. L., Denardo, G. L., DeNardo, S. J., Mirick, G. R., Miers, L. A., Greiner, D. P., & Meares, C. F. (1995). Effect of the extent of chelate substitution on the immunoreactivity and biodistribution of 2IT-BAT-Lym-1 immunoconjugates. Cancer Research, 55(4), 878-884.

Effect of the extent of chelate substitution on the immunoreactivity and biodistribution of 2IT-BAT-Lym-1 immunoconjugates. / Kukis, D. L.; Denardo, Gerald L; DeNardo, S. J.; Mirick, G. R.; Miers, L. A.; Greiner, D. P.; Meares, C. F.

In: Cancer Research, Vol. 55, No. 4, 1995, p. 878-884.

Research output: Contribution to journalArticle

Kukis, DL, Denardo, GL, DeNardo, SJ, Mirick, GR, Miers, LA, Greiner, DP & Meares, CF 1995, 'Effect of the extent of chelate substitution on the immunoreactivity and biodistribution of 2IT-BAT-Lym-1 immunoconjugates', Cancer Research, vol. 55, no. 4, pp. 878-884.
Kukis, D. L. ; Denardo, Gerald L ; DeNardo, S. J. ; Mirick, G. R. ; Miers, L. A. ; Greiner, D. P. ; Meares, C. F. / Effect of the extent of chelate substitution on the immunoreactivity and biodistribution of 2IT-BAT-Lym-1 immunoconjugates. In: Cancer Research. 1995 ; Vol. 55, No. 4. pp. 878-884.
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abstract = "Trial therapy for lyphoma with the radiolabeled chelate-antibody conjugate 67Cu-2IT-BAT-Lym-1 has been promising. It is desirable to deliver therapeutic doses of radiometal using a minimum amount of 2IT-BAT-Lym-1 to minimize the risks of adverse patient reaction and antigenic response to antibody. This is readily accomplished by increasing the number of metal- binding sites (i.e., chelating agents) conjugated per antibody, but the ability of the antibody to bind antigen and target tumor cells in vivo must not be impaired by the conjugation reaction. To determine the maximum chelator:antibody ratio (c/a) of 2IT-BAT-Lym-1 at which functional integrity is preserved, immunoconjugates with a c/a of 1.3-23 were prepared and examined by radioimmunoassay and competitive antigen binding versus lightly iodinated Lym-1. The biodistribution in rumored mice of conjugates with c/a of 2.1, 4.3, 8.4, and 11.4 also was examined. Conjugates with c/a up to 5 exhibited no loss of immunoreactivity, and conjugates with c/a up to 11 retained 75{\%} or greater immunoreactivity relative to unmodified Lym-1. All conjugates examined competed less effectively than did unmodified Lym-1 for antigen binding, but the effect at c/a 5 was slight. Tumor uptake declined with increasing c/a, but the effect was insignificant at c/a 2.1 and 4.3. Conjugates of c/a 4-5 were found to be optimal for the preparation of radioimmunoconjugate of high specific activity with minimal, if any, loss of functional integrity.",
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AU - Mirick, G. R.

AU - Miers, L. A.

AU - Greiner, D. P.

AU - Meares, C. F.

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