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. 1999 Dec 8;82(1):56–64. doi: 10.1054/bjoc.1999.0877

Targeted photodestruction of human colon cancer cells using charged Dougherty chlorine6immunoconjugates

M Del Governatore 1,2, MR Hamblin 1, EE Piccinini 2, G Ugolini 2, T Hasan 1
PMCID: PMC2363172  PMID: 10638967

Abstract

The goal of this study was to develop a strategy for the selective destruction of colorectal cancer cells. Towards this end, photoimmunoconjugates were prepared between the anti-colon cancer monoclonal antibody 17.1A and the photosensitizer (PS) chlorine6(ce6). Polylysine linkers bearing several ce6molecules were covalently attached in a site-specific manner to partially reduced IgG molecules, which allowed photoimmunoconjugates to bear either cationic or anionic charges. The conjugates retained immunoreactivity as shown by enzyme-linked immunosorbent assays and by competition studies with native antibody. The overall charge on the photoimmunoconjugate was an important determinant of PS delivery. The cationic photoimmunoconjugate delivered 4 times more ce6to the cells than the anionic photoimmunoconjugate, and both 17.1A conjugates showed, in comparison to non-specific rabbit IgG conjugates, selectivity for antigen-positive target cells. Illumination with only 3 J cm−2of 666 nm light reduced the number of colony forming cells by more than 90% for the cationic 17.1A conjugate and by 73% for the anionic 17.1A conjugate after incubation with 1 μM ce6equivalent of the respective conjugates. By contrast, 1 μM free ce6gave only a 35% reduction in colonies. These data suggest photoimmunoconjugates may have applications in photoimmunotherapy where destruction of colorectal cancer cells is required. © 2000 Cancer Research Campaign

Keywords: photodynamic therapy, photoimmunotherapy, photosensitizer, polylysine, laser

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Selected References

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