Methods and compositions for diagnosis and treatment of cancer
The present invention relates to the identification of nucleic acid and amino acid sequences that are characteristic of tumor tissues such as ovarian tumor and lung tumor tissues and which represent targets for therapy or diagnosis of tumor diseases in a subject.
1. A method for diagnosis, detecting or monitoring, and treating of a tumor disease comprising the steps of:
detecting the presence of or determining the quantity of a nucleic acid which codes for a peptide comprising the amino acid sequence of a tumor antigen, in a biological sample isolated from a patient,
wherein said tumor antigen comprises an amino acid sequence encoded by a nucleic acid sequence which comprises SEQ ID NO: 1, and
diagnosing, detecting, or monitoring the tumor disease based on the presence or quantity of the nucleic acid comprising the nucleic acid sequence of SEQ ID NO: 1 in the biological sample, wherein
the detecting or determining comprises
(i) contacting the biological sample with an agent that binds specifically to the nucleic acid within the nucleic acid sequence of SEQ ID NO:1 or to a nucleic acid sequence which is complementary to said nucleic acid sequence, so as to form a complex comprising said agent; and
(ii) detecting the formation of, or determining the quantity of, the complex formed, wherein said agent is an oligonucleotide or polynucleotide that hybridizes specifically to the nucleic acid or to the complementary nucleic acid sequence, and has a nucleic acid sequence selected from the group consisting of SEQ ID NO:6 and SEQ ID NO:7;
wherein an increased amount of the complex in the biological sample of the patient as compared to a normal sample of an individual without a tumor disease indicates the patient has the tumor disease;
wherein the tumor disease is selected from the group consisting of ovarian cancer, ovarian adenocarcinoma, ovarian teratocarcinoma, lung cancer, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), lung carcinoma, lung adenocarcinoma, gastric cancer, breast cancer, hepatic cancer, pancreatic cancer, skin cancer, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, head and neck cancer, malignant pleomorphic adenoma, sarcoma, synovial sarcoma, synovial carcinosarcoma, bile duct cancer, renal cell carcinoma, renal clear cell carcinoma, renal papillary cell carcinoma, uterine cancer, cancer of the urinary bladder, papillary carcinoma, colon cancer, transitional cell carcinoma small bowel cancer, cancer of the ileum, small bowel adenocarcinoma, adenocarcinoma of the ileum, testicular embryonal carcinoma, placental choriocarcinoma, cervical cancer, testicular cancer testicular seminoma, testicular teratoma, embryonic testicular cancer, and the metastatic forms thereof; and
administering a pharmaceutical composition to the patient if the increased amount of the complex in the biological sample of the patient is detected, wherein the pharmaceutical composition comprises an antibody binding to the tumor antigen.
2. A method for detecting and treating circulating tumor cells in a patient comprising the steps of:
detecting the presence of or determining the quantity of a nucleic acid which codes for a peptide comprising the amino acid sequence of a tumor antigen in a biological sample containing or suspected of containing disseminating or circulating tumor cells or metastatic tumor cells isolated from said patient,
wherein said tumor antigen comprises an amino acid sequence encoded by a nucleic acid sequence which comprises SEQ ID NO: 1, and
detecting the circulating tumor cells based on the presence or quantity of the nucleic acid comprising SEQ ID NO:1 in the biological sample, wherein
the detecting comprises
(i) contacting the biological sample with an agent that binds specifically to the nucleic acid within the nucleic acid sequence of SEQ ID NO:1 or to a nucleic acid sequence which is complementary to said nucleic acid sequence, so as to form a complex comprising said agent; and
(ii) detecting the formation of, or determining the quantity of, the complex formed, wherein said agent is an oligonucleotide or polynucleotide that hybridizes specifically to the nucleic acid or to the complementary nucleic acid sequence, and has a nucleic acid sequence selected from the group consisting of SEQ ID NO:6 and SEQ ID NO:7;
wherein an increased amount of the complex in the biological sample of the patient as compared to a normal sample of an individual without a tumor disease detects the circulating tumor cells; and
administering a pharmaceutical composition to the patient if the increased amount of the complex in the biological sample of the patient is detected, wherein the pharmaceutical composition comprises an antibody binding to the tumor antigen.
3. A method of detecting and treating metastatic ovarian cancer cells or metastatic lung cancer cells in a patient comprising the steps of:
detecting the presence of or determining the quantity of a nucleic acid which codes for a peptide comprising the amino acid sequence of a tumor antigen in a biological sample isolated from a tissue or organ of said patient wherein when the tissue or organ is free of tumors cells in the sample do not substantially express said nucleic acid or peptide,
wherein the nucleic acid or peptide is not substantially expressed if the level of expression is lower compared to expression in placenta cells or placenta tissue and/or is lower compared to expression in ovarian tumor cells and/or lung tumor cells or ovarian tumor tissue and/or lung tumor tissue, or if the level of expression is below the detection limit,
wherein said tumor antigen comprises an amino acid sequence encoded by a nucleic acid sequence which comprises SEQ ID NO: 1, and
detecting the cancer cells based on the presence or quantity of the nucleic acid comprising the nucleic acid sequence of SEQ ID NO:1 in the biological sample, wherein
the detecting or determining comprises
(i) contacting the biological sample with an agent that binds specifically to the nucleic acid within the nucleic acid sequence of SEQ ID NO:1 or to a nucleic acid sequence which is complementary to said nucleic acid sequence, so as to form a complex comprising said agent; and
(ii) detecting the formation of, or determining the quantity of, the complex formed, wherein said agent is an oligonucleotide or polynucleotide that hybridizes specifically to the nucleic acid or to the complementary nucleic acid sequence, and has a nucleic acid sequence selected from the group consisting of SEQ ID NO:6 and SEQ ID NO:7;
wherein an increased amount of the complex in the biological sample of the patient as compared to a normal sample of a healthy individual indicates the presence of metastatic ovarian cancer cells or metastatic lung cancer cells; and
administering a pharmaceutical composition to the patient if the increased amount of the complex in the biological sample of the patient is detected, wherein the pharmaceutical composition comprises an antibody binding to the tumor antigen.
4. The method as claimed in any of claims 1 to 2 , wherein the biological sample is from a tissue or organ wherein when the tissue or organ is free of tumors, cells in the sample do not substantially express said tumor antigen and/or a nucleic acid encoding said tumor antigen,
wherein the nucleic acid or peptide is not substantially expressed if the level of expression is lower compared to expression in placenta cells or placenta tissue and/or is lower compared to expression in ovarian tumor cells and/or lung tumor cells or ovarian tumor tissue and/or lung tumor tissue, or if the level of expression is below the detection limit.
5. The method as claimed in any of claims 1 to 3 , wherein the nucleic acid sequence of SEQ ID NO:6 or SEQ ID NO:7 further comprises a detectable label.
6. The method as claimed in any of claim 1 , 2 , or 3 , wherein the tumor antigen comprises the amino acid sequence according to SEQ ID NO: 2.
7. The method of claim 1 , wherein the detection of and/or determination of the quantity of the nucleic acid comprises RT-PCR analysis or Northern blot analysis.
8. The method of claim 7 , wherein the RT-PCR analysis comprises a pair of oligonucleotides comprising SEQ ID NOs:6 and 7.
9. A method for diagnosis, detecting or monitoring, and treating a tumor disease comprising the steps of:
detecting the presence of or determining the quantity of a nucleic acid which codes for a peptide comprising the amino acid sequence of a tumor antigen, in a biological sample isolated from a patient,
wherein said tumor antigen comprises an amino acid sequence encoded by a nucleic acid sequence which comprises SEQ ID NO: 1, and
diagnosing, detecting, or monitoring the tumor disease based on the presence or quantity of the nucleic acid comprising the nucleic acid sequence of SEQ ID NO:1 in the biological sample, wherein
the detecting or determining comprises
(i) contacting the biological sample with an agent that binds specifically to the nucleic acid within the nucleic acid sequence of SEQ ID NO:1 or to a nucleic acid sequence which is complementary to said nucleic acid sequence, so as to form a complex comprising said agent; and
(ii) detecting the formation of, or determining the quantity of, the complex formed, wherein said agent is an oligonucleotide or polynucleotide that hybridizes specifically to the nucleic acid or to the complementary nucleic acid sequence;
wherein an increased amount of the complex in the biological sample of the patient as compared to a normal sample of an individual without a tumor disease indicates the patient has the tumor disease;
wherein the tumor disease is selected from the group consisting of ovarian cancer, ovarian adenocarcinoma, ovarian teratocarcinoma, lung cancer, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), lung carcinoma, lung adenocarcinoma, gastric cancer, breast cancer, hepatic cancer, pancreatic cancer, skin cancer, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, head and neck cancer, malignant pleomorphic adenoma, sarcoma, synovial sarcoma, synovial carcinosarcoma, bile duct cancer, renal cell carcinoma, renal clear cell carcinoma, renal papillary cell carcinoma, uterine cancer, cancer of the urinary bladder, papillary carcinoma, colon cancer, transitional cell carcinoma small bowel cancer, cancer of the ileum, small bowel adenocarcinoma, adenocarcinoma of the ileum, testicular embryonal carcinoma, placental choriocarcinoma, cervical cancer, testicular cancer testicular seminoma, testicular teratoma, embryonic testicular cancer, and the metastatic forms thereof; and
administering a pharmaceutical composition to the patient if the increased amount of the complex in the biological sample of the patient is detected, wherein the pharmaceutical composition comprises an antibody binding to the tumor antigen.
10. A method of detecting and treating metastatic ovarian cancer cells or metastatic lung cancer cells in a patient comprising the steps of:
detecting the presence of or determining the quantity of a nucleic acid which codes for a peptide comprising the amino acid sequence of a tumor antigen in a biological sample isolated from a tissue or organ of said patient wherein when the tissue or organ is free of tumors cells in the sample do not substantially express said nucleic acid or peptide,
wherein the nucleic acid or peptide is not substantially expressed if the level of expression is lower compared to expression in placenta cells or placenta tissue and/or is lower compared to expression in ovarian tumor cells and/or lung tumor cells or ovarian tumor tissue and/or lung tumor tissue, or if the level of expression is below the detection limit,
wherein said tumor antigen comprises an amino acid sequence encoded by a nucleic acid sequence which comprises SEQ ID NO: 1, and
detecting the cancer cells based on the presence or quantity of the nucleic acid comprising the nucleic acid sequence of SEQ ID NO:1 in the biological sample, wherein
the detecting or determining comprises
(i) contacting the biological sample with an agent that binds specifically to the nucleic acid within the nucleic acid sequence of SEQ ID NO:1 or to a nucleic acid sequence which is complementary to said nucleic acid sequence, so as to form a complex comprising said agent; and
(ii) detecting the formation of, or determining the quantity of, the complex formed, wherein said agent is an oligonucleotide or polynucleotide that hybridizes specifically to the nucleic acid or to the complementary nucleic acid sequence;
wherein an increased amount of the complex in the biological sample of the patient as compared to a normal sample of a healthy individual indicates the presence of metastatic ovarian cancer cells or metastatic lung cancer cells; and
administering a pharmaceutical composition to the patient if the increased amount of the complex in the biological sample of the patient is detected, wherein the pharmaceutical composition comprises an antibody binding to the tumor antigen.
11. The method as claimed in any of claim 1 , 2 , 3 , 9 or 10 , wherein the antibody is coupled to a therapeutic agent.
12. The method as claimed in any of claim 1 , 2 , 3 , 9 or 10 wherein the pharmaceutical composition comprises a ligand of the tumor nucleic acid or the tumor antigen.
13. The method of claim 2 , wherein the tumor disease is selected from the group consisting of ovarian cancer, ovarian adenocarcinoma, ovarian teratocarcinoma, lung cancer, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), lung carcinoma, lung adenocarcinoma, gastric cancer, breast cancer, hepatic cancer, pancreatic cancer, skin cancer, basal cell carcinoma, squamous cell carcinoma, malignant melanoma, head and neck cancer, malignant pleomorphic adenoma, sarcoma, synovial sarcoma, synovial carcinosarcoma, bile duct cancer, renal cell carcinoma, renal clear cell carcinoma, renal papillary cell carcinoma, uterine cancer, cancer of the urinary bladder, papillary carcinoma, colon cancer, transitional cell carcinoma small bowel cancer, cancer of the ileum, small bowel adenocarcinoma, adenocarcinoma of the ileum, testicular embryonal carcinoma, placental choriocarcinoma, cervical cancer, testicular cancer testicular seminoma, testicular teratoma, embryonic testicular cancer, and the metastatic forms thereof.