We report a single institution phase I trial of chimeric (mouse-human)
monoclonal antibody (chL6) directed against a
tumor-associated
cell surface antigen expressed in non-small cell lung, colon, and
breast cancer. The results of the study were contrasted with a previous trial of murine L6.
ChL6 was administered intravenously to 18 patients with advanced
cancer as a single, 4-16 infusion in doses ranging from 350 mg/m2 to 700 mg/m2. One patient received four weekly doses of 350 mg/m2. Patients were followed for side effects, localization of antibody to
tumor cells, pharmacokinetics and the development of
antibodies against
chL6. Side effects associated with treatment were
chills,
fever, and
nausea, which lasted 24-48 hours. Platelet count and absolute leukocyte count fell immediately
after treatment, but returned to pretreatment levels by day 7. Localization of
chL6 to
tumor cells in vivo was seen at 350 mg/m2 and "saturation" at 700 mg/m2 and 350 mg/m2 per week x 4. The pharmacokinetics of this antibody appeared similar to its murine analogue. Human
antibodies against
chL6 were detected in only 4 of 18 patients. These
antibodies were directed against murine variable regent and their titers were lower than those occurring in most patients who received murine L6 in an earlier trial. No
tumor reductions were seen. Chimeric L6 appears to be a suitable antibody for delivering anti-
tumor agents because of its low immunogenicity and favorable in vivo
tumor binding characteristics.