Targeted photodestruction of human colon cancer cells using charged 17.1A chlorin(e6) immunoconjugates

The goal of this study was to develop a strategy for the selective destruct ion of colorectal cancer cells. Towards this end, photoimmunoconjugates wer e prepared between the anti-colon cancer monoclonal antibody 17.1A and the photosensitizer (PS) chlorin, (c(e6)). Polylysine linkers bearing several c (e6) molecules were covalently attached in a site-specific manner to partia lly reduced IgG molecules, which allowed photoimmunoconjugates to bear eith er cationic or anionic charges. The conjugates retained immunoreactivity as shown by enzyme-linked immunosorbent assays and by competition studies wit h native antibody. The overall charge on the photoimmunoconjugate was an im portant determinant of PS delivery. The cationic photoimmunoconjugate deliv ered 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 wi th only 3 J cm(-2) of 666 nm light reduced the number of colony forming cel ls by more than 90% for the cationic 17.1A conjugate and by 73% for the ani onic 17.1A conjugate after incubation with 1 mu M c(e6) equivalent of the r espective conjugates. By contrast. 1 mu M free c(e6) gave only a 35% reduct ion in colonies. These data suggest photoimmunoconjugates may have applicat ions in photoimmunotherapy where destruction of colorectal cancer cells is required. (C) 2000 Cancer Research Campaign.