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Published on: September 14, 2010
Monoclonal antibody KS1/4-methotrexate immunoconjugate studies in non-small cell lung carcinoma
D J Elias1, L E Kline, B A Robbins
1Department of Molecular and Experimental Medicine, Ida M. And Cecil H. Green Cancer Center, Scripps Clinic and Research Foundation, La Jolla, California 92037.
Abstract:
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.
Insights
This study evaluated KS1/4-methotrexate (KS1/4-MTX) for advanced non-small cell lung cancer. The immunoconjugate showed feasibility and potential usefulness, with some patients experiencing tumor reduction and MAb KS1/4 binding.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacology
Background:
- The KS1/4 antigen is present on epithelial malignancies and some normal tissues.
- Targeted drug delivery aims to improve cancer treatment efficacy.
Purpose of the Study:
- To evaluate the safety and potential efficacy of the KS1/4-methotrexate (KS1/4-MTX) immunoconjugate.
- To assess the feasibility of using monoclonal antibody (MAb) KS1/4 for targeted chemotherapy in non-small cell lung carcinoma.
Main Methods:
- Eleven patients with advanced non-small cell lung carcinoma received escalating doses of KS1/4-MTX.
- Toxicities and treatment responses were monitored.
- Post-treatment tumor biopsies assessed MAb KS1/4 binding.
Main Results:
- The maximal tolerated dose was 1,750 mg/M2 with a cumulative methotrexate (MTX) dose of 40 mg/M2.
- Common toxicities included fever, nausea, vomiting, and diarrhea.
- One patient showed a 50% decrease in lung nodules; four patients developed a human antimouse antibody response.
- Tumor biopsies confirmed MAb KS1/4 binding.
Conclusions:
- KS1/4-MTX demonstrates feasibility for treating non-small cell lung carcinoma.
- The study highlights the potential of MAb-directed chemotherapy for targeting tumor-associated antigens.
- Further investigation is warranted to optimize this targeted therapy approach.
