Melanoma antigens and their use in diagnostic and therapeutic methods
AssigneeThe United States of America as represented by the Department of Health and Human Services
InventorsYutaka Kawakami, Steven A. Rosenberg
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Abstract
The present invention provides a nucleic acid sequence encoding a melanoma antigen recognized by T lymphocytes, designated MART-1. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess or prognoses a mammal afflicted with melanoma or metastata melanoma. This invention also provides immunogenic peptides derived from the MRT-1 melanoma antigen and a second melanoma antigen designated gp100. This invention further provides immunogenic peptides derived from the MART-1 melanoma antigen or gp100 antigen which have been modified to enhance their immunogenicity. The proteins and peptides provided can serve as an immunogen or vaccine to prevent or treat melanoma.
Claims11
A vector comprising a nucleic acid encoding an immunogenic peptide consisting of 5-20 contiguous amino acids of gp100 (SEQ ID NO:
- 27) with at least one amino acid modification in the 5-20 contiguous amino acids of SEQ ID NO:
- 27, wherein the immunogenic peptide reacts with T-lymphocytes and said modification is an amino acid substitution located at an amino acid position of the immunogenic peptide selected from the group consisting of:
- (i) the first position, (ii) the second position, (iii) the third position, (iv) the ninth position, (v) tenth position, and (vi) combinations of at least two of (i)-(v), wherein the immunogenic peptide is not YIEPGPVTA (SEQ ID NO:
- 134).
A vector comprising an isolated nucleic acid encoding an immunogenic peptide comprising an amino acid sequence of the formula selected from the group consisting of X1X2X3 GQYWQX4 (SEQ ID NO:
- 123), X1X2X3QVPFSX4 (SEQ ID NO:
- 124) and X1X2X3PGPVTX4 (SEQ ID NO:
- 125), wherein:
- X1 is selected from the group consisting of methionine, leucine, alanine, glycine, threonine, isoleucine, valine, tyrosine, serine, tryptophan, phenylalanine, lysine and aspartic acid;
- X2 is any hydrophobic aliphatic amino acid when the immunogenic peptide comprises an amino acid sequence of the formula X1X2X3GQYWQX4 (SEQ ID NO:
- 123) or X1X2X3QVPFSX4 (SEQ ID NO:
- 124);
- X2 is selected from the group consisting of methionine, leucine, alanine, glycine, valine and threonine when the immunogenic peptide comprises an amino acid sequence of the formula X1X2X3PGPVTX4 (SEQ ID NO:
- 125);
- X3 is any naturally occurring amino acid;
- and X4 is any hydrophobic aliphatic amino acid,
- wherein the immunogenic peptide is not KTWGQYWQV (SEQ ID NO:
- 46), KTWGQYWQVL (SEQ ID NO:
- 47), ITDQVPFSV (SEQ ID NO:
- 48), or YLEPGPVTA (SEQ ID NO:
- 40).
Dependencies are inferred from the claim text.