Am. J. Respir. Crit. Care Med., Vol 150, No. 4, Oct 1994, 1114-1122.
Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non- small cell lung carcinoma
DJ Elias, LE Kline, BA Robbins, HC Johnson Jr, K Pekny, M Benz, JA Robb, LE Walker, M Kosty and RO Dillman
Department of Molecular and Experimental Medicine, Ida M. And Cecil H. Green Cancer Center, Scripps Clinic and Research Foundation, La Jolla, California 92037.
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.
