Evaluation of monoclonal antibodies for the development of breast cancer immunotoxins
Eighty-five antibodies recognizing breast cancer-selective antigens were conjugated to ricin toxin A-chain using a disulfide linkage. The cytotoxicities of the resulting immunotoxins were determined on breast cancer cells and normal human fibroblasts. Twenty-four antibodies formed immunotoxins that were toxic to at least one breast cancer cell line at concentrations of 10 nM or less but were nontoxic to human fibroblast lines used as negative controls. Some of the breast tumor-selective immunotoxins were as toxic as a conjugate between monoclonal anti-transferrin receptor and ricin toxin A-chain (50% inhibition of cellular protein synthesis at approximately 0.1 nM). Another set of four immunotoxins were indiscriminately toxic to human breast tumor cell lines, two human fibroblast cell lines, and a human lymphoblastoid line. Several of the antibodies the toxin conjugates of which specifically killed breast cancer cell lines may be useful in cancer therapy, since they show a wide range of binding to individual breast tumors and cell lines and a limited range of binding to normal tissue types.
- Research Organization:
- Cetus Corp., Emeryville, CA
- OSTI ID:
- 5612282
- Journal Information:
- Cancer Res.; (United States), Journal Name: Cancer Res.; (United States) Vol. 45:3; ISSN CNREA
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMAL CELLS
ANTIBODIES
ANTIGENS
BODY
CASTOR
CELL CULTURES
CELL KILLING
CHROMATOGRAPHY
CONNECTIVE TISSUE CELLS
DIAGNOSTIC USES
EXPERIMENTAL NEOPLASMS
FIBROBLASTS
GLANDS
IMMUNOTHERAPY
ISOTOPE APPLICATIONS
ISOTOPES
LIQUID COLUMN CHROMATOGRAPHY
MAMMARY GLANDS
MATERIALS
MEDICINAL PLANTS
MONOCLONAL ANTIBODIES
ORGANS
PLANTS
SEPARATION PROCESSES
SOMATIC CELLS
SULFUR ISOTOPES
THERAPY
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
USES