Preparation of recombinant protein A-lymphotoxin chimeric protein and its antitumor effects in mice

We have investigated the in vivo function of a chimeric protein constructed by recombinant DNA techniques. The behavior and antitumor activity of a protein A-lymphotoxin chimera (ALT) was examined on a murine tumor in mice in comparison with amino-terminal 19 amino acid-deleted lymphotoxin (dLT). Seven-week-old male BALB/c mice were implanted intradermally with Meth-A fibrosarcoma on day 0. ALT and dLT caused tumor regression, hemorrhagic necrosis and complete regression in a dose-related way when each agent was given intratumorally 5 times (days 5-9). The ratio of the median effective doses for complete tumor regression was 1.6 between ALT and dLT on a molar basis. ALT caused tumor regression and body weight loss when given intravenously on the same schedule. Biodistribution studies with 125I-labeled ATL and dLT demonstrated that, after intratumoral administration, ALT was retained longer in the administered site and was cleared more slowly from the mouse body than dLT. These findings suggest that a protein A-lymphotoxin chimeric protein expresses both antitumor activity similar to that of lymphotoxin and characteristic in vivo behavior of the fused protein A portion.