Peptides and combination of peptides for use in immunotherapy against prostate cancer and other cancers
The present invention relates to peptides, proteins, 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 T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.
1. A method for producing an antibody specifically binding to a human major histocompatibility complex (MHC) class I molecule complexed with a HLA-restricted antigen consisting of the amino acid sequence of SEQ ID NO: 24, comprising:
(a) immunizing a genetically engineered non-human mammal comprising cells expressing said MHC class I molecule with a soluble form of a MHC class I molecule complexed with an HLA-restricted antigen consisting of the amino acid sequence of SEQ ID NO: 24;
(b) isolating mRNA molecules from antibody producing cells of said non-human mammal;
(c) producing a phage display library displaying protein molecules encoded by said mRNA molecules;
(d) isolating at least one phage from said phage display library,
wherein said at least one phage displaying said antibody specifically binding to said MHC class molecule complexed with an HLA-restricted antigen consisting of the amino acid sequence of SEQ ID NO: 24; and
(e) preparing said antibody using said phage display.
2. The method of claim 1 , wherein the antibody binds to said MHC class I molecule complexed with an antigen consisting of the amino acid sequence of SEQ ID NO: 24 with a binding affinity of below 20 nanomolar.
3. The method of claim 1 , further comprising humanizing the antibody.
4. The method of claim 1 , further comprising conjugating the antibody with a toxin.
5. The method of claim 1 , further comprising conjugating the antibody with an immune stimulating domain.
6. The method of claim 1 , wherein the antibody is a monoclonal antibody.
7. The method of claim 1 , further comprising modifying the antibody to a bi-specific antibody.
8. The method of claim 1 , further comprising modifying the antibody to a chimeric antibody.
9. The method of claim 1 , wherein the non-human mammal is mouse.
10. The method of claim 1 , wherein the MHC class I molecule is HLA-A*24.
11. The method of claim 1 , further comprising labeling the antibody with a radionucleotide.
12. The method of claim 11 , wherein the radionucleotide is selected from the group consisting of 111 In, 99 Tc, 14 C, 131 I, 3 H, 32 P, and 35 S.
13. The method of claim 1 , wherein the antibody has an affinity value (Kd) of less than 1×10 μM.
14. The method of claim 1 , further comprising modifying the antibody to an Fv.
15. The method of claim 1 , further comprising modifying the antibody to an Fab.
16. The method of claim 1 , further comprising modifying the antibody to an Fab′.
17. The method of claim 1 , wherein the antibody binds to said MHC class I molecule complexed with an antigen consisting of the amino acid sequence of SEQ ID NO: 24 with a binding affinity of below 10 nanomolar.