Methods for diagnosis and therapy for pancreatic cancer and composition useful therein

Abstract: Polynucleotide and polypeptide UKW are specific for pancreatic tumors. Diagnosis of UKW is therefore valuable for diagnosis of pancreatic tumors. Antibodies against UKW are, besides their value in diagnosis, useful as therapeutic agents for the treatment of pancreatic tumors. (end of abstract)

Methods for diagnosis and therapy for pancreatic cancer and composition useful therein description/claims

Brief Patent Description

Full Patent Description

Patent Application Claims

PRIORITY TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No. 10/696,487, filed Oct. 29, 2003, now pending; which claims the benefit of European Application No. 02024539.5 filed Oct. 31, 2002. The entire contents of the above-identified applications are hereby incorporated by reference.

BACKGROUND OF THE INVENTION

The present invention generally relates to methods for diagnosis of pancreatic cancer, compositions useful therefore and therapeutic methods for the treatment of pancreatic cancer.

Pancreatic cancer is a cancer type which is difficult to diagnose and to control and most of such cancers can grow very rapidly.

Neoplasms of the exocrine pancreas may arise from ductal, acinar and stromal cells. Eighty percent of pancreatic carcinomas are derived from ductal epithelium. 60% of these tumors are located in the head of the pancreas, 10% in the tail and 30% are located in the body of the pancreas or are diffuse (Warshau, A. L., and Fernandez-del, C. C., N. Engl. J. Med. 326 (1992) 4555-4565). Histologically, these tumors are graded as well as differentiated, moderately differentiated and poorly differentiated. Some tumors are classified as adenosquamous, mucinous, undifferentiated or undifferentiated with osteoblast-like giant cells (Gibson, J. B., and Sobin, L. H., Histological typing of tumors of the liver, biliary tract and pancreas, WHO, Geneva, 1978). Since the disease is asymptomatic in its early stages, because of the lack of any test for early diagnosis and due to its aggressive character with respect to metastasis locally and to visceral organs, this disease is associated with a dismal prognosis. Only 20% of the tumors are resectable and the survival benefit of approved chemotherapy regiments is rather poor (Kroep, J. R., et al., Ann. Oncol. 10, Suppl. 4 (1999) 234-238). Identification of new targets for early diagnosis of pancreatic tumors is therefore a challenge of paramount importance.

WO 02/08288 describes secreted and transmembrane polypeptides and nucleic acids encoding the same. FIG. 130 shows the polypeptide sequence of UKW.

SUMMARY OF THE INVENTION

It was surprisingly found that nucleic acids coding for polypeptide UKW are overexpressed specifically in pancreatic tumor cells, whereas expression is considerably lower in normal pancreatic cells or in tumor cells of other origin, e.g., breast cancer or colon cancer cells. Therefore, UKW is a valuable new target for specific diagnosis and therapy of pancreatic cancer.

According to one aspect of the present invention, a method for determining the presence or absence of pancreatic cancer in a patient comprises

(i) obtaining a biological sample from a patient;
(ii) detecting in the sample an amount of nucleic acid encoding UKW or an amount of polypeptide UKW; and
(iii) comparing the amount of nucleic acid or polypeptide with a predetermined standard value indicating the decision line for tumor-induced or non-tumor-induced UKW expression or presence in the cell and therefrom determining the presence or absence of pancreatic cancer in the patient.

Preferably, the detection is performed by the use of a binding agent which binds to UKW nucleic acid or polypeptide. More preferably, the binding agent is a probe hybridizing under stringent conditions with UKW nucleic acid or an antibody, preferably a monoclonal antibody binding to UKW polypeptide, preferably to the extracellular domain.

According to another aspect of the present invention, there is provided a process for determining whether or not a test sample of tissue or fluid of a patient contains pancreatic tumor cells or is derived from pancreatic tumor cells, wherein the test sample and a second sample originating from non-pancreatic-tumor cells from the same individual or a different individual of the same species are used, which process comprises the following steps:

(a) incubating each respective sample under stringent hybridization conditions with a nucleic acid probe which is selected from the group consisting of: