NOVEL IMMUNOTHERAPY AGAINST SEVERAL TUMORS INCLUDING NEURONAL AND BRAIN TUMORS
The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to 30 peptide sequences and their variants derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.
1 . A method of treating a patient who has cancer, comprising administering to the patient an effective amount of an antibody specifically binding to an MHC class I or II molecule complexed with a HLA-restricted antigen consisting of the amino acid sequence of KIQEILTQV (SEO ID NO: 14), wherein the cancer is selected from the group consisting of glioblastoma, renal cell carcinoma, melanoma, endometrial cancer, esophageal squamous cell carcinoma, pancreatic cancer, and urothelial cancer.
2 . The method of claim 1 , wherein the antibody is a polyclonal antibody, a monoclonal antibody, or a chimeric antibody.
3 . The method of claim 1 , wherein the antibody binds to the HLA-restricted antigen with a binding affinity of below 20 nanomolar.
4 . The method of claim 1 , wherein the antibody binds to the MHC class I molecule complexed with the HLA-restricted antigen.
5 . The method of claim 1 , wherein the antibody is humanized.
6 . The method of claim 1 , wherein the effective amount of the antibody is from about 1 μg/kg to about 100 mg/kg of body weight per day.
7 . The method of claim 1 , wherein the antibody is conjugated with a toxin.
8 . The method of claim 7 , wherein the toxin is selected from the group consisting of diptheria toxin, pseudomonas exotoxin A, cholera toxin, and ricin toxin.
9 . A method of diagnosing cancer in a subject, comprising
administering to the subject an antibody specifically binding to an MHC class I or II molecule complexed with a HLA-restricted antigen consisting of the amino acid sequence of KIQEILTQV (SEO ID NO: 14),
wherein the antibody is labeled with a radionucleotide,
detecting the radionucleotide, and
localizing the cancer using immunoscintiography, wherein the cancer is selected from the group consisting of glioblastoma, renal cell carcinoma, melanoma, endometrial cancer, esophageal squamous cell carcinoma, pancreatic cancer, and urothelial cancer.
10 . The method of claim 9 , wherein the antibody is a polyclonal antibody, a monoclonal antibody, or a chimeric antibody.
11 . The method of claim 9 , wherein the antibody has an affinity value (Kd) of less than 1×10 μM.
12 . The method of claim 9 , wherein the antibody binds to the MHC class I molecule complexed with the HLA-restricted antigen.
13 . The method of claim 9 , wherein the antibody is humanized.
14 . The method of claim 9 , wherein the radionucleotide is selected from the group consisting of 111 In, 99 Tc, 14 C, 131 I, 3 H, 32 P, 35 S.
15 . The method of claim 9 , wherein the immunoscintiography is positron emission tomography (PET).
16 . The method of claim 1 , wherein the cancer is glioblastoma.
17 . The method of claim 9 , wherein the cancer is glioblastoma.
18 . A method for producing an antibody specifically binding to a human major histocompatibility complex (MHC) class I or II molecule complexed with an HLA-restricted antigen consisting of the amino acid sequence of KIQEILTQV (SEO ID NO: 14), comprising
immunizing a genetically engineered non-human mammal comprising cells expressing said MHC class I or II molecule with a soluble form of an MHC class I or II molecule complexed with said HLA-restricted antigen,
isolating mRNA molecules from antibody producing cells of said non-human mammal,
producing a phage display library displaying protein molecules encoded by said mRNA molecules, and
isolating at least one phage from said phage display library,
wherein said at least one phage displays said antibody specifically binding to said MHC class I or II molecule complexed with said HLA-restricted antigen.
19 . The method of claim 1 , wherein the antibody is a polyclonal antibody, a monoclonal antibody, or a chimeric antibody.
20 . The method of claim 1 , wherein the antibody binds to the HLA-restricted antigen with a binding affinity of below 20 nanomolar.
21 . The method of claim 1 , wherein the antibody binds to the MHC class I molecule complexed with the HLA-restricted antigen.
22 . The method of claim 1 , further comprising humanizing the antibody.