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US 10,137,144 B2Granted
Methods and compositions for the activation of gamma-delta T-cells
AssigneeAmerican Gene Technologies International Inc.
InventorsCharles David Pauza, Haishan Li, Tyler Lahusen, Mei-Ling Liou
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Abstract
The present invention relates generally to methods and compositions for gene therapy and immunotherapy that activate gamma delta T-cells, and in particular, can be used in the treatment of various cancers and infectious diseases.
Claims20
A method of treating a cancer in a subject using an immunotherapy-based composition, the method comprising:
- administering a therapeutically-effective amount of an bisphosphonate drug to the subject;
- and
- administering a therapeutically-effective amount of the immunotherapy-based composition to the subject,
- wherein the immunotherapy-based composition comprises a lentiviral particle, the lentiviral particle comprising:
- a. an envelope protein capable of infecting one or more cancer cells, and
- b. at least one encoded shRNA capable of inhibiting production of an enzyme of the mevalonate pathway, wherein the at least one encoded shRNA comprises a sequence having at least 80% percent identity with:
- i.
- (SEQ ID NO:
- 1)
- GTCCTGGAGTACAATGCCATTCTCGAGAATGGCATTGTACTCCA
- GGACTTTTT;
- ii.
- (SEQ ID NO:
- 2)
- GCAGGATTTCGTTCAGCACTTCTCGAGAAGTGCTGAACGAAATC
- CTGCTTTTT;
- iii.
- (SEQ ID NO:
- 3)
- GCCATGTACATGGCAGGAATTCTCGAGAATTCCTGCCATGTACA
- TGGCTTTTT;
- or
- iv.
- (SEQ ID NO:
- 4)
- GCAGAAGGAGGCTGAGAAAGTCTCGAGACTTTCTCAGCCTCCT
- TCTGCTTTTT;
- or
- c. at least one encoded microRNA capable of inhibiting production of an enzyme of the mevalonate pathway, wherein the at least one encoded microRNA comprises a sequence having at least 80% percent identity with:
- i.
- (SEQ ID NO:
- 5)
- AAGGTATATTGCTGTTGACAGTGAGCGACACTTTCTCAGCCTCC
- TTCTGCGTGAAGCCACAGATGGCAGAAGGAGGCTGAGAAAGTG
- CTGCCTACTGCCTCGGACTTCAAGGGGCT;
- ii.
- (SEQ ID NO:
- 6)
- AAGGTATATTGCTGTTGACAGTGAGCGACACTTTCTCAGCCTCC
- TTCTGCGTGAAGCCACAGATGGCAGAAGGGCTGAGAAAGTGCT
- GCCTACTGCCTCGGACTTCAAGGGGCT;
- iii.
- (SEQ ID NO:
- 7)
- TGCTGTTGACAGTGAGCGACTTTCTCAGCCTCCTTCTGCGTGAA
- GCCACAGATGGCAGAAGGAGGCTGAGAAAGTTGCCTACTGCCT
- CGGA;
- iv.
- (SEQ ID NO:
- 8)
- CCTGGAGGCTTGCTGAAGGCTGTATGCTGACTTTCTCAGCCTCC
- TTCTGCTTTTGGCCACTGACTGAGCAGAAGGGCTGAGAAAGTC
- AGGACACAAGGCCTGTTACTAGCACTCA;
- v.
- (SEQ ID NO:
- 9)
- CATCTCCATGGCTGTACCACCTTGTCGGGACTTTCTCAGCCTCC
- TTCTGCCTGTTGAATCTCATGGCAGAAGGAGGCGAGAAAGTCT
- GACATTTTGGTATCTTTCATCTGACCA;
- or
- vi.
- (SEQ ID NO:
- 10)
- GGGCCTGGCTCGAGCAGGGGGCGAGGGATACTTTCTCAGCCTC
- CTTCTGCTGGTCCCCTCCCCGCAGAAGGAGGCTGAGAAAGTCCT
- TCCCTCCCAATGACCGCGTCTTCGTCG.
63 more elements
A pharmaceutical combination comprising:
- a bisphosphonate compound;
- and
- a lentiviral particle produced by a packaging cell and capable of infecting a target cell, the lentiviral particle comprising an envelope protein capable of infecting the target cell, and:
- a. at least one encoded shRNA capable of inhibiting production of an enzyme of the mevalonate pathway, wherein the at least one encoded shRNA comprises a sequence having at least 80% percent identity with:
- i.
- (SEQ ID NO:
- 1)
- GTCCTGGAGTACAATGCCATTCTCGAGAATGGCATTGTACTCCA
- GGACTTTTT;
- ii.
- (SEQ ID NO:
- 2)
- GCAGGATTTCGTTCAGCACTTCTCGAGAAGTGCTGAACGAAATC
- CTGCTTTTT;
- iii.
- (SEQ ID NO:
- 3)
- GCCATGTACATGGCAGGAATTCTCGAGAATTCCTGCCATGTACA
- TGGCTTTTT;
- or
- iv.
- (SEQ ID NO:
- 4)
- GCAGAAGGAGGCTGAGAAAGTCTCGAGACTTTCTCAGCCTCCT
- TCTGCTTTTT;
- or
- b. at least one encoded microRNA capable of inhibiting production of an enzyme of the mevalonate pathway, wherein the at least one encoded microRNA comprises a sequence having at least 80% percent identity with:
- v.
- (SEQ ID NO:
- 5)
- AAGGTATATTGCTGTTGACAGTGAGCGACACTTTCTCAGCCTCC
- TTCTGCGTGAAGCCACAGATGGCAGAAGGAGGCTGAGAAAGTG
- CTGCCTACTGCCTCGGACTTCAAGGGGCT;
- vi.
- (SEQ ID NO:
- 6)
- AAGGTATATTGCTGTTGACAGTGAGCGACACTTTCTCAGCCTCC
- TTCTGCGTGAAGCCACAGATGGCAGAAGGGCTGAGAAAGTGCT
- GCCTACTGCCTCGGACTTCAAGGGGCT;
- vii.
- (SEQ ID NO:
- 7)
- TGCTGTTGACAGTGAGCGACTTTCTCAGCCTCCTTCTGCGTGAA
- GCCACAGATGGCAGAAGGAGGCTGAGAAAGTTGCCTACTGCCT
- CGGA;
- viii.
- (SEQ ID NO:
- 8)
- CCTGGAGGCTTGCTGAAGGCTGTATGCTGACTTTCTCAGCCTCC
- TTCTGCTTTTGGCCACTGACTGAGCAGAAGGGCTGAGAAAGTC
- AGGACACAAGGCCTGTTACTAGCACTCA;
- ix.
- (SEQ ID NO:
- 9)
- CATCTCCATGGCTGTACCACCTTGTCGGGACTTTCTCAGCCTCC
- TTCTGCCTGTTGAATCTCATGGCAGAAGGAGGCGAGAAAGTCT
- GACATTTTGGTATCTTTCATCTGACCA;
- or
- x.
- (SEQ ID NO:
- 10)
- GGGCCTGGCTCGAGCAGGGGGCGAGGGATACTTTCTCAGCCTC
- CTTCTGCTGGTCCCCTCCCCGCAGAAGGAGGCTGAGAAAGTCCT
- TCCCTCCCAATGACCGCGTCTTCGTCG;
- wherein the pharmaceutical combination is at least one of fixed and non-fixed.
62 more elements
Dependencies are inferred from the claim text.