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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) chlorin(e6) (c(e6)). Polylysine linkers bearing several c(e6) molecules 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 c(e6) to 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(-2) of 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 microM c(e6) equivalent of the respective conjugates. By contrast, 1 microM free c(e6) gave only a 35% reduction in colonies. These data suggest photoimmunoconjugates may have applications in photoimmunotherapy where destruction of colorectal cancer cells is required.

Targeted photodestruction of human colon cancer cells using charged 17.1A chlorine6 immunoconjugates