Therapeutic use of Anti-tf-antigen antibody

Abstract

The invention is related to administration of monoclonal antibody JAA-F11 to an individual for inhibition of metastasis and / or inhibition of growth of cells which express TF—Ag, or for detection of tumors or metastatic foci which express TF—Ag. For inhibition of metastasis or inhibition of growth of cells expressing TF—Ag, the method comprises administering to the individual a therapeutic amount of mAb JAA-F11, wherein the JAA-F11 mAb inhibits the metastasis and / or growth of the TF—Ag expressing cancer cells. For detection of tumors or metastatic foci, mAb JAA-F11 is conjugated to a detectable label and administered to the individual. Detection of the label identifies metastatic foci or tumors which comprise cancer cells expressing TF—Ag.

Description

[0001]This application is a Divisional of U.S. application Ser. No. 11 / 190,165, filed on Jul. 26, 2005, which in turn claims priority to U.S. provisional application No. 60 / 591,011, filed on Jul. 26, 2004, the disclosures of each of which are incorporated herein by reference.[0002]This invention was supported by grant number R15AI49210-01 from the National Institutes of Health. The Government has certain rights in the invention.FIELD OF THE INVENTION[0003]The present invention relates generally to the inhibition of cancer cell growth and metastasis. More particularly, the invention relates to the use of a monoclonal antibody to inhibit metastasis of cancer cells in an individual.BACKGROUND OF THE INVENTION[0004]During carcinogenesis, alterations occur in the biosynthesis of carbohydrate structures on the cell surface, and several different carbohydrates linked either to proteins or to lipids have been recognized to be tumor-associated antigens. TF-Antigen (TF—Ag) is a tumor-associat...

AI Technical Summary

Benefits of technology

JAA-F11 effectively inhibits cancer cell adhesion, growth, and metastasis, as demonstrated by reduced nodule formation in lungs and prolonged survival in mouse models, with specific binding to cancer cells and minimal reaction with normal tissues, offering a more mature immune response and improved therapeutic outcomes.

Problems solved by technology

However, IgM is generally of lower affinity and specificity than IgG, and represents a less mature immune response, and many previous studies relating to antibodies to TF—Ag involve IgM antibodies.

Further, some anti-TF—Ag antibodies are not clinically useful because they cause undesirable proliferation of tumor cells (45).

Moreover, while peptides which can bind to TF—Ag and inhibit cell adhesion in vitro have been described (5), it has also been found that some peptides which can bind to the TF—Ag on human carcinoma cell lines and interfere with cell aggregation exhibit a low monomeric affinity for the TF—Ag, and therefore cannot be dissolved at high concentration in aqueous buffers, which significantly limit their potential use (Landon et al., Journal of Protein Chemistry, (2003) Vol. 22: pp 193-204).

While there were fewer nodules in mice receiving the pre-incubated cells, this study did not provide a relevant model of antibody-mediated inhibition of metastasis because, due to the pre-incubation of the cancer cells with the monoclonal antibody, there was no requirement for the antibody to travel through the body to locate and bind to cells expressing the TF—Ag.

Further, there was no assessment as to whether the nodule formation was the result of cancer cells traveling through the endothelium in a manner similar to the natural metastatic process or whether the nodules were simply the result of lodging and proliferation of the injected cells.

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