Phase I trial of chimeric (human-mouse) monoclonal antibody L6 in patients with non-small-cell lung, colon, and breast cancer.
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.
Goodman
G E
GE
Swedish Hospital Tumor Institute, Seattle, WA 98104.
Hellstrom
I
I
Yelton
D E
DE
Murray
J L
JL
O'Hara
S
S
Meaker
E
E
Zeigler
L
L
Palazollo
P
P
Nicaise
C
C
Usakewicz
J
J
D000328:Adult; D000368:Aged; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D001943:Breast Neoplasms / Q000628:therapy*; D002277:Carcinoma / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000628:therapy*; D003110:Colonic Neoplasms / Q000628:therapy*; D003176:Complement C3 / Q000378:metabolism; D003181:Complement C4 / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000628:therapy*; D051379:Mice; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D003176:Complement C3; D003181:Complement C4; D011993:Recombinant Fusion Proteins