Tumor localization by combinations of monoclonal antibodies in a new human colon carcinoma cell line (LIM1899)

Journal Article · Sat Sep 01 04:00:00 EDT 1990 · Cancer Research; (USA)

OSTI ID:6759474

Andrew, S M; Teh, J G; Johnstone, R W; Russell, S M; Whitehead, R H; McKenzie, I F; Pietersz, G A ^[1]

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1. Univ. of Melbourne, Parkville, Victoria (Australia)

One of the problems of in vivo diagnosis and therapy of tumors with monoclonal antibodies is their heterogeneity with respect to antigen expression, with some cells expressing no antigen and others being weakly or strongly positive. Selected mixtures of antibodies to different antigens are therefore likely to react with more cells than single antibodies and be more effective for imaging and therapy. With this in mind, we have examined a new human colon cancer cell line (LIM1899) which has a heterogeneous expression of several cell surface molecules: by flow cytometry 38% were carcinoembryonic antigen positive; 64%, human milk fat globule positive, and 73%, CD46 positive; 87% of tumor cells bound a mixture of all three antibodies in vitro. Some blocking of the binding of anti-human milk fat globule antibody by the anti-CD46 antibody was noted. LIM1899 was established as a xenograft in nude mice and in vivo biodistribution studies performed using antibodies alone or in combination. Mixtures of antibodies clearly showed a higher percentage of injected dose of antibody in the tumor than did single antibodies: one antibody gave 10%; two together, 17 to 21%; and all three together gave 29% of the injected dose in the tumor. Tumor:blood ratios were also superior for combinations of antibodies, provided that low doses of the antibodies were used; at higher doses the effect was lost. The study demonstrates that combinations of antibodies are better than single antibodies for localization, provided that the dose used is carefully selected.

• OSTI ID: 6759474
• Journal Information: Cancer Research; (USA), Journal Name: Cancer Research; (USA) Vol. 50:17; ISSN CNREA; ISSN 0008-5472
• Country of Publication: United States
• Language: English

Related Subjects

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62 RADIOLOGY AND NUCLEAR MEDICINE
ANIMALS
ANTIBODIES
ANTIGENS
BIOLOGICAL LOCALIZATION
BODY
CARCINOEMBRYONIC ANTIGEN
CARCINOMAS
CELL FLOW SYSTEMS
COUNTING TECHNIQUES
DIAGNOSTIC TECHNIQUES
DIGESTIVE SYSTEM
DISEASES
EXPERIMENTAL NEOPLASMS
GASTROINTESTINAL TRACT
IMMUNOLOGY
IMMUNOTHERAPY
INTESTINES
ISOTOPE APPLICATIONS
LARGE INTESTINE
MAMMALS
MEDICINE
MICE
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEAR MEDICINE
ORGANS
RADIOIMMUNODETECTION
RADIOIMMUNOLOGY
RADIOIMMUNOSCINTIGRAPHY
RADIOIMMUNOTHERAPY
RADIOISOTOPE SCANNING
RADIOLOGY
RADIOTHERAPY
RODENTS
SCINTISCANNING
SPECIFICITY
THERAPY
TRACER TECHNIQUES
VERTEBRATES