Tumor-associated peptides binding promiscuously to human leukocyte antigen (HLA) class II molecules
The present invention relates to immunotherapeutic methods, and molecules and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumour-associated T-helper cell peptide epitopes, alone or in combination with other tumour-associated peptides, that serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumour immune responses. In particular, the present invention relates to 49 novel peptide sequences derived from HLA class II molecules of human tumour cell lines which can be used in vaccine compositions for eliciting anti-tumour immune responses.
1. An activated cytotoxic T lymphocyte (CTL) expressing an exogenous single chain T cell receptor (TCR) that binds to a peptide consisting of the amino acid sequence of SQDDIKGIQKLYGKRS (SEQ ID NO: 33) in a complex with a class II MHC molecule, produced by a method comprising
introducing a retroviral vector encoding the TCR into a CTL, and
contacting in vitro the CTL with the peptide loaded unto human class II MHC molecules expressed on the surface of a suitable antigen-presenting cell for a period of time sufficient to activate said CTL in an antigen specific manner,
wherein the CTL selectively recognizes a cell that aberrantly expresses the peptide,
wherein the TCR is integrated in the genome of the CTL.
2. The activated CTL of claim 1 , wherein the peptide has the ability to bind human major histocompatibility complex (MHC) class-II molecule HLA-DRB*0101 and has the ability to bind to at least one additional molecule of the human major histocompatibility complex (MHC) class-II.
3. The activated CTL of claim 1 , wherein the peptide is a fusion protein, comprising N-terminal amino acids of the HLA-DR antigen-associated invariant chain (Ii).
4. The activated CTL of claim 1 , wherein the cell overexpresses the peptide at a level at least 1.2-fold more than a normal cell.
5. The activated CTL of claim 1 , wherein the antigen-presenting cell is a dendritic cell.
6. The activated CTL of claim 1 , wherein the antigen-presenting cell is an artificial antigen-presenting cell.
7. The activated CTL of claim 1 , wherein the TCR is expressed by an expression vector capable of expressing a nucleic acid encoding the TCR.
8. The activated CTL of claim 1 , wherein the TCR comprises a VαJ segment followed by VβDJ segment followed by β chain constant region (Cβ) segment.