Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes
AssigneeThe United States of America as represented by the Secretary of Health and Human Services
InventorsRong Fu Wang, Steven A. Rosenberg
Life of this patent
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Abstract
The infusion of TIL586 along with interleukin-2 (IL-2) into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. A gene encoding a tumor antigen recognized by TIL586 was previously isolated and shown to encode gp75 or TRP-1. The present invention relates to the identification of a second tumor antigen recognized by a HLA-A31 restricted CTL clone derived from the TIL586 cell line. This antigen derived from the TRP-2 protein tumor antigen and peptides thereof are capable of sensitizing target cells for lysis by a CTL clone at 1 nM peptide concentration. Modified peptides were also recognized by the CTL clone.
Claims74
A composition comprising an isolated tumor antigen, which comprises the amino acid sequence LLGPGRPYR (SEQ ID NO;
- 4), wherein said isolated tumor antigen stimulates cancer antigen specific T lymphocytes that are restricted by the HLA-A31 MHC Class I molecule, and a physiologically acceptable carTier, excipient, or diluent.
The composition according to clam/, wherein the co-immunostimulatory molecule is an MEC molecule.
A composition comprising an isolated tumor antigen consisting of a polypeptide encoded by nucleic acids 836–1045 of SEQ ID NO:
- 1, wherein said antigen stimulates cancer specific T lymphocytes that are restricted by the HLA-A31 MHC Class I molecule, and a physiologically acceptable carrier, excipient, or diluent.
A composition comprising an isolated twnor antigen, which comprises a functionally equivalent variant of the amino acid sequence LLGPGRPYR (SEQ ID NO:
- 4), wherein the functionally equivalent variant consists essentially of an amino acid sequence that has at least 85% sequence homology with SEQ ID NO:
- 4, wherein said isolated tumor antigen stimulates cancer antigen specific T lymphocytes that are restricted by the HLA-A31 MHC Class I molecule, and a physiologically acceptable carrier, excipient, or diluent.
The composition of claim wherein the functionally equivalent variant is LAGPGRPYR (SEQ ID NO:
- 10).
A composition comprising an isolated tumor antigen, wherein said antigen has an amino acid sequence which is a fragment of SEQ ID NO:
- 2 and which comprises the amino acid sequence LLGPGRPR (SEQ ID NO:
- 4), wherein said fragment stimulates cancer antigen specific T lymphocytes that are restricted by the HLA-A31 MHC Class I molecule, and a physiologically acceptable carrier, excipient, or diluent.
The method of claim wherein the host is a mammal.
Dependencies are inferred from the claim text.