Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non-small cell lung carcinoma.
The antigen reactive with murine monoclonal antibody (MAb) KS1/4 is expressed on epithelial malignancies and some normal epithelial tissues. Studies were undertaken to evaluate KS1/4-methotrexate (KS1/4-MTX) immunoconjugate in patients with advanced non-small cell carcinoma of the lung. Eleven patients in two different groups received KS1/4-MTX in two different escalating dose infusion schedules with a maximal tolerated dose of 1,750 mg/M2 and a cumulative dose of MTX of 40 mg/M2. Toxicities were similar in both groups and included fever, anorexia, nausea, vomiting, diarrhea, abdominal pain, guaiac positive stool, and hypoalbuminemia. Two patients had an associated aseptic meningitis. One patient had a 50% decrease in two lung nodules without a change in lymphangitic infiltrates. This patient received a second course of treatment and developed an immune complex-mediated arthritis and serum sickness. Four patients mounted a human antimouse antibody response. Post-treatment tumor biopsies documented binding of MAb KS1/4. These studies document the feasibility and potential usefulness of a MAb directed against tumor-associated antigens with the targeting of chemotherapeutic drugs in patients with non-small cell lung carcinoma.
Elias
D J
DJ
Department of Molecular and Experimental Medicine, Ida M. And Cecil H. Green Cancer Center, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Kline
L E
LE
Robbins
B A
BA
Johnson
H C
HC
Pekny
K
K
Benz
M
M
Robb
J A
JA
Walker
L E
LE
Kosty
M
M
Dillman
R O
RO
D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D000951:Antigens, Neoplasm / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015815:Cell Adhesion Molecules; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D000071858:Epithelial Cell Adhesion Molecule; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008727:Methotrexate / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics; D008875:Middle Aged
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; D018796:Immunoconjugates; D007074:Immunoglobulin G; D008727:Methotrexate