P53-specific T cell receptor for adoptive immunotherapy
AssigneeCity of Hope
InventorsJoshua D. I. Ellenhorn, Don J. Diamond
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Abstract
The present invention relates to molecular cloning of cDNA for both A and B chains of hu p53-specific, HLA restricted mu TCR, transfer of the cDNA to hu T cells, and functional expression of the p53-specific TCR in hu CTLs. The functional expression of the mu TCR results in the recognition of endogenously processed hu p53 expressed in tumor cells. The invention thus also relates to an anti-cancer immunotherapy by the adoptive transfer of TCR gene modified autologous T cells.
Claims8
An isolated nucleic acid which encodes a human p53 specific HLA restricted murine T-cell receptor (TCR), wherein said nucleic acid comprises
- (a) a polynucleotide encoding the A chain of a hu p53-specific, HLA restricted mu T cell receptor (TCR), said A chain having the amino acid sequence set forth in SEQ ID NO:19;
- and
- (b) a polynucleotide encoding the B chain of a hu p53-specific, HLA restricted mu TCR, said B chain having the amino acid sequence set forth in SEQ ID NO:21.
An isolated nucleic acid selected from the group consisting of:
- (a) a polynucleotide encoding the A chain of a hu p53-specific, HLA restricted mu T cell receptor (TCR), said A chain having the amino acid sequence set forth in SEQ ID NO:19;
- and
- (b) a polynucleotide encoding the B chain of a hu p53-specific, HLA restricted mu TCR, said B chain having the amino acid sequence set forth in SEQ ID NO:21.
An isolated hu CD8+ cytotoxic T lymphocyte which is transfected with one or more nucleic acids which express a hu p53-specific, HLA restricted mu TCR, wherein said nucleic acids comprise
- (a) a polynucleotide encoding the A chain of a hu p53-specific, HLA restricted mu T cell receptor (TCR), said A chain having the amino acid sequence set forth in SEQ ID NO:19;
- and
- (b) a polynucleotide encoding the B chain of a hu p53-specific, HLA restricted mu TCR, said B chain having the amino acid sequence set forth in SEQ ID NO:21.
Dependencies are inferred from the claim text.