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, in particular tumors of the central nervous system (CNS) such as glioma, in particular glioblastoma and which represent targets for therapy or diagnosis of tumor diseases in a subject.
1. A method for diagnosis, detection or monitoring of a glioblastoma characterized by expression of a tumor antigen, the method comprising the detection of and/or determination of the quantity of one or more parameters selected from the group consisting of:
(i) a nucleic acid which codes for said tumor antigen or a tumor antigen peptide derived from said tumor antigen,
(ii) a peptide comprising the amino acid sequence of said tumor antigen or of a tumor antigen peptide derived from said tumor antigen,
(iii) an antibody which binds to a peptide comprising the amino acid sequence of said tumor antigen or of a tumor antigen peptide derived from said tumor antigen,
(iv) a T cell that recognizes a peptide comprising the amino acid sequence of said tumor antigen or of a tumor antigen peptide derived from said tumor antigen, and
(v) a cell which presents a peptide comprising the amino acid sequence of said tumor antigen peptide derived from 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 which comprises the nucleic acid sequence according to SEQ ID NO: 1 or 2 of the sequence listing and said tumor antigen peptide comprises an amino acid sequence corresponding to the amino acid sequence of a fragment of said tumor antigen, wherein said tumor antigen peptide comprises at least 6 consecutive amino acids of said tumor antigen, wherein the presence of the nucleic acid, peptide, antibody, T cell, or cell in the biological sample or an increased quantity of the nucleic acid, peptide, antibody, T cell, or cell in the biological sample compared to a reference level is indicative of glioblastoma.
2. The method as claimed in claim 1 , wherein the biological sample is from a tissue or organ wherein the cells when the tissue or organ is free of tumors do not substantially express said tumor antigen and/or a nucleic acid encoding said tumor antigen.
3. The method as claimed in claim 1 , wherein the detection and/or determination of the quantity comprises:
(i) contacting the biological sample with an agent which binds specifically to the nucleic acid, the peptide, the antibody, the T cell or the cell which is to be detected and/or the quantity of which is to be determined, and
(ii) detecting the formation of and/or determining the quantity of a complex between the agent and the nucleic acid, the peptide, the antibody, the T cell or the cell which is to be detected or the quantity of which is to be determined.
4. The method as claimed in claim 3 , wherein (i) the agent which binds specifically to the nucleic acid comprises an oligonucleotide, which hybridizes specifically to said nucleic acid, (ii) the agent which binds specifically to the peptide comprises an antibody binding specifically to said peptide, (iii) the agent which binds specifically to the antibody comprises a peptide binding specifically to said antibody, or (iv) the agent which binds specifically to the T cell comprises a cell presenting a complex between an MHC molecule and the peptide comprising the amino acid sequence of a tumor antigen peptide derived from said tumor antigen.
5. The method as claimed in claim 3 , wherein the agent further comprises a detectable label.
6. A method for detecting expression or activity of COL20A1 in a patient suspected of having glioblastoma or having a potential for developing glioblastoma, the method comprising:
(i) obtaining a biological sample from the patient;
(ii) detecting or quantifying (a) a nucleic acid which codes for a COL20A1 protein or a fragment thereof, or (b) COL20A1 protein or a fragment thereof in the sample, wherein the COL20A1 protein has an amino acid sequence of SEQ ID NO: 3 or SEQ ID NO: 4 and wherein the fragment comprises at least 6 consecutive amino acids of the COL20A1 protein.
7. The method as claimed in claim 6 , wherein step (ii) comprises: contacting the biological sample with an agent which binds specifically to the nucleic acid and detecting the formation of and/or determining the quantity of a complex between the agent and the nucleic acid.
8. The method as claimed in claim 7 , wherein the agent which binds specifically to the nucleic acid comprises an oligonucleotide that hybridizes specifically to the nucleic acid.
9. The method as claimed in claim 8 , wherein the oligonucleotide comprises a detectable label.
10. The method as claimed in claim 6 , wherein step (ii) comprises: contacting the biological sample with an agent which binds specifically to the protein or fragment thereof and detecting the formation of and/or determining the quantity of a complex between the agent and the protein or fragment thereof.
11. The method as claimed in claim 10 , wherein the agent which binds specifically to the protein or fragment thereof comprises an antibody.
12. The method as claimed in claim 11 , wherein the antibody comprises a detectable label.
13. The method as claimed in claim 6 , wherein the patient has glioblastoma.