Selenocystamine, a superoxide generating selenium (Se) compound has been covalently conjugated to a B72.3 Mab forming a Mab-Se immunoconjugate generating superoxide in the presence of glutathione. The B72.3 Mab Se-immunoconjugate retained its LS174T colon tumor cell binding activity as indicated by an ELISA assay. A [3H]-thymidine incorporation assay indicated that the cytotoxicity of the B72.3 Mab-Se immunoconjugate was not as great as selenocystamine alone. The B72.3 Mab-Se immunoconjugate, native B72.3 Mab, selenocystamine and PBS (control) were used to treat athymic nude mice inoculated with 106 LS174 T colon human colon cancer cells. Thirty-three days after tumor cell inoculation and following treatments the detectable tumor incidence in mice with Mab-Se immunoconjugate was 62.5% (5/8), native B72.3 Mab 100% (8/8). selenocystamine 100% (7/7) and PBS 100% (7/7). The B72.3 Mab-Se immunoconjugate was seen to have a greater inhibitory effect on tumor growth in the athymic nude mice over the 33 day treatment period as indicated by a calculated least mean tumor volume among all groups. This report is believed to be the first use of an anti-tumor Mab targeting selenium's free radical activity to treat cancer in vivo. The results show promise of a therapeutic strategy of site specific superoxide generated toxicity by attachment of Se to tumor specific monoclonal antibodies.
|State||Published - 1997|