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Monoclonal antibodies against human colon carcinoma-associated antigens and uses therefor

a human colon carcinoma and antibody technology, applied in the field of immunology and medicine, can solve the problem that none of the sakamoto mabs has the degree of colon tumor specificity, and achieve the effect of improving the survival rate of cancer patients and enhancing the host anti-tumor immunity

Inactive Publication Date: 2007-08-07
INT BIO IMMUNE SYST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0032]The present invention is also directed to the above-discussed colon carcinoma-associated antigens which are unique in that (1) the epitopes recognized by the mAbs are of the protein and not the carbohydrate component of tumor-associated glycoproteins; (2) the antigens are not expressed in normal tissues; (3) the antigens are tumor-specific, being present in the malignancies of colon, breast and ovarian cancer; (4) the antigens are immunogenic in humans, having the capability of enhancing host anti-tumor immunity, thus improving survival in cancer patients; and (5) the immunogenicity in humans is specific, in that only colon, breast and ovarian cancer patients, but not patients with other forms of cancer, show evidence of specific in vivo or in vitro immunological reactivity to the antigens.

Problems solved by technology

Furthermore, none of the Sakamoto mAbs have the degree of colon tumor specificity of the mAbs disclosed in the present application.

Method used

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  • Monoclonal antibodies against human colon carcinoma-associated antigens and uses therefor
  • Monoclonal antibodies against human colon carcinoma-associated antigens and uses therefor
  • Monoclonal antibodies against human colon carcinoma-associated antigens and uses therefor

Examples

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Effect test

example i

Preparation and Characterization of the Colon Carcinoma-Associated Antigen (CCAA)

[0168]The antigenic preparation was obtained from pooled colon carcinoma membranes according to the method described by Hollinshead et al., Cancer 56:480 (1985). This antigenic material was purified to the extend that the membrane fractions were free of HL-A antigens and were separated from much of the non-immunogenic glycoprotein fractions. In its final form the antigenic preparation was shown to be immunogenic in a specific manner in humans as evidenced by its capability of eliciting a delayed hypersensitivity reaction only in patients with active colon, breast, and ovary carcinoma.

[0169]Tumor cell suspensions in saline were prepared from fresh operating room specimens. Single cell suspensions, obtained by conventional means, were centrifuged for 10 minutes at about 400×g and the supernatant was retained. The cell pellet was resuspended and recentrifuged. The membrane material was examined by electron...

example ii

Preparation and Screening of Monoclonal Antibodies

[0172]Monoclonal antibodies (mAbs) against human colon carcinoma-associated antigens (CCAA) were obtained by the production and cloning of hybrids resulting from the fusion of mouse myeloma cells Sp2 / 0-Ag14 with spleen cells from BALB / c mice which had been immunized with the CCAA described above.

[0173]Five hybrid clones were established, as described below, and designated as 31.2, 31.1, 77, 33.23 and 33.28. All five mAbs reacted strongly with the CCAA and with two colon carcinoma cell lines (SW480 and SW620) when assayed by ELISA. Two of the mAbs, 31.1. and 33.28, were studied in greatest detail.

A. Immunization and Cell Fusion

[0174]BALB / c mice were immunized by intrapertioneal injection of 50 μg of the CCAA described above emulsified in complete Freud's adjuvant, as described by Hollinshead in clinical trials (Hollinshead et al., supra). Ten days later the mice received an intravenous booster injection of the same amount of CCAA in s...

example iii

Analysis of Monoclonal Antibodies and their Reactivity

[0178]The anti-CCAA mAbs produced and detected as above were also tested for reactivity with fresh human tissue. Cryostat sections of the tissue types listed in Table 2, below, were fixed with 3.5% formaldehyde in PBS and then washed three times with PBS. For indirect immunofluorescence studies, the sections were incubated with the mAbs and then stained with a fluorescein-labelled second antibody as above.

[0179]As is shown in Table 2, mAbs 31.1 and 33.28 were highly specific for colon carcinoma cells. This indicates that an antigen (CCAA) which was highly specific for colon carcinoma and, furthermore, was immunogenic in colon carcinoma patients (positive DH reactions), and served as a successful immunogen in mice for the devnd phycoerythrin excitation was used. Trigger regions were established by examining cells by forward versus 90° light scatter. As shown in Table 4, both 31.1 and 33.28 bound to colon carcinoma cells; neither m...

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Abstract

Monoclonal antibodies, in particular 33.28 and 31.1, and chimeric antibodies, in particular mouse / humans chimeric Chi #1 specific for glycoprotein antigens of colon carcinoma-associated antigens which are immunogenic in humans, are disclosed. Such antibodies, and fragments and derivatives thereof, are useful in immunodiagnosis and immunotherapy of human colon, breast, and ovarian cancer, and for purification of antigens which can serve as immunotherapeutic agents. Methods of detecting the colon carcinoma-associated antigen in a sample, and methods for treating subjects having colon, breast, and ovarian carcinomas are disclosed.

Description

[0001]This application is a continuation-in-part of U.S. application Ser. No. 08 / 159,836 filed Nov. 30, 1993, which is a continuation-in-part of U.S. application Ser. No. 08 / 117,430, filed Sep. 7, 1993, now abandoned, which is a continuation-in-part of U.S. application Ser. No. 07 / 670,816, filed Mar. 18, 1991, now abandoned, which is a continuation-in-part of U.S. application Ser. No. 07 / 176,337, filed Mar. 31, 1988, now abandoned.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]This invention, in the field of immunology and medicine, relates to new hybridoma lines and the monoclonal antibodies (mAbs) they secrete which are specific for clinically defined colon carcinoma-associated antigens. The mAbs are useful in vivo for immunodetection and immunotherapy of colon carcinoma as well as for the detection and purification of colon carcinoma-associated antigens.[0004]2. Description of the Background Art[0005]During the process of oncogenesis, a number of cell-surface mol...

Claims

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Application Information

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IPC IPC(8): G01N33/574C07K16/18C07K16/30G01N33/53
CPCC07K16/3046C07K2317/732G01N33/57419
Inventor TSANG, KWONG Y.ARLEN, MYRON
Owner INT BIO IMMUNE SYST
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