Pancreatic cancer associated antigen, antibody thereto, and diagnostic and treatment methods
First Claim
1. A pancreatic carcinoma-specific antigen 3C4-Ag in substantially purified form characterized by:
- a molecular weight of about 43.5 kDa as determined by SDS-PAGE;
a pI on isoelectrofocusing of about 4.5 to about 5.0;
being unglycosylated or minimally glycosylated; and
being primarily localized on the surface of rat and human pancreatic cancer cells but not detected in normal, non-proliferating cells.
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Abstract
The present invention is directed to an antigen found on the surface of rat and human pancreatic cancer cells and provides antibodies of high specificity and selectivity to this antigen as well as hybridomas secreting the subject antibodies. Methods for both the diagnosis and treatment of pancreatic cancer are also provided. This tissue marker of pancreatic adenocarcinoma, an approximately 43.5 kD surface membrane protein designated PaCa-Ag1, is completely unexpressed in normal pancreas but abundantly expressed in pancreatic carcinoma cells. Moreover, a soluble form of PaCa-Ag1 exists, having a molecular weight about 36 to about 38 kD, that is readily identified in sera and other body fluids of pancreatic cancer patients, using a subject antibody.
88 Citations
24 Claims
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1. A pancreatic carcinoma-specific antigen 3C4-Ag in substantially purified form characterized by:
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a molecular weight of about 43.5 kDa as determined by SDS-PAGE;
a pI on isoelectrofocusing of about 4.5 to about 5.0;
being unglycosylated or minimally glycosylated; and
being primarily localized on the surface of rat and human pancreatic cancer cells but not detected in normal, non-proliferating cells. - View Dependent Claims (3, 8)
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2. A soluble pancreatic carcinoma-specific antigen 3C4-Ag having a molecular weight of about 36 to about 38 kD as determined by SDS-PAGE and isolatable from sera and other bodily fluids of pancreatic cancer patients.
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4. An antibody or binding portion thereof, having binding specificity to pancreatic carcinoma specific antigen 3C4-Ag, wherein said antigen is characterized by:
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a molecular weight of about 43 kDa as determined by SDS-PAGE;
a pI on isoelectrofocusing of about 4.5 to about 5.0;
being unglycosylated or minimally glycosylated; and
being primarily localized on the surface of rat and human pancreatic cancer cells but not detected in normal, non-proliferating cells. - View Dependent Claims (5, 6, 7, 9, 10, 11, 12, 13, 14, 15, 16, 17)
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18. A method of detecting pancreatic cancer in an animal subject, said method comprising the steps of:
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(a) contacting a cell, tissue or fluid sample from the subject with at least one of an antibody or binding portion thereof which specifically binds to 3C4-Ag or an immunologically active fragment thereof;
the monoclonal antibody mAb34C;
or an antibody which binds the epitope bound by the monoclonal antibody mAb34C;
under conditions permitting said antibody to specifically bind an antigen in the sample to form an antibody-antigen complex;
(b) detecting antibody-antigen complex in the sample; and
(c) correlating the detection of elevated levels of antibody-antigen complex in the sample with the presence of pancreatic cancer.
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19. A diagnostic kit suitable for detecting 3C4-Ag in a cell, tissue, or fluid sample from a patient, said kit comprising:
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(a) an antibody or binding portion thereof which specifically binds 3C4-Ag or an immunologically active fragment thereof, (b) a conjugate of a specific binding partner for-the-antibody or binding portion thereof; and
(c) a label for detecting the bound antibody.
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- 20. A method of treating pancreatic cancer in a patient suffering therefrom which comprises administering to the patient an effective amount of an antibody or binding portion thereof which specifically binds to 3C4-Ag or an immunologically active fragment thereof, wherein said antibody or binding portion thereof is conjugated or linked to a therapeutic drug or toxin.
- 23. A pharmaceutical composition comprising an antibody or binding portion thereof which specifically binds to 3C4-Ag, admixed with a pharmaceutically acceptable carrier.
Specification