Monoclonal antibody-chromophore conjugates as selective phototoxins

Tayyaba Hasan, Albert Lin, David Yarmush, Alan Oseroff, Martin Yarmush

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

he chromophore chlorin e6 monoethylene diamine monoamide (CMA) was bound via poly(glutamic acid) (PGA) to two monoclonal antibodies (Mabs), an anti bovine serum albumin (BSA) Mab designated 9.1 and an anti-Leu-1 Mab. The final ratio of chromophore to Mab was dependent on the starting concentration of the chromophore. Binding activity and specificity, determined using 125I-labeled Mab, showed 70% retention at CMA:Mab ratios of 36. Singlet oxygen quantum yields relative to rose bengal, estimated from the bleaching of N,N->dimethylnitrosoaniline, were the same for CMA free or bound to Mab. When Mab 9.1 was conjugated to a diamino cyanine, 1,1′-(3-propylamine hydrobromide)-3,3,3′,3′-tetramethylindotricarbocyanine (TCC), the resultant conjugates were highly aggregated, presumably due to crosslinking via the two amino groups. When anti-Leu-1 target cells, HPB-ALL T-leukemia cells treated with the conjugate were exposed to broad-band, long wavelength irradiation and cell survival evaluated by fluorescence microscopy, a radiant-exposure-dependent phototoxicity was observed. Cells treated similarly with chlorin e6, buffer or Mab alone were unaffected. At the concentrations used in these experiments, neither CMA nor anti-Leu-1 were toxic in the absence of light. These results suggest that conjugates having high chromophore to Mab ratios can be prepared using PGA, and that these conjugates may find use as potential photochemotherapeutic agents.

Original languageEnglish (US)
Pages (from-to)107-117
Number of pages11
JournalJournal of Controlled Release
Volume10
Issue number1
DOIs
StatePublished - Oct 1989

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Keywords

  • chromophore
  • conjugate
  • monoclonal antibody
  • photochemotherapy
  • photosensitization
  • poly(glutamic acid)

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