Combination vectors and methods for treating cancer
A composition for treating cancer is disclosed. The composition includes a lentiviral particle and an aminobisphosphonate drug. The lentiviral particle is capable of infecting a target cell, such as a cancer cell, and includes an envelope protein optimized for targeting such target cell and a viral vector. The viral vector includes a small RNA optimized to target an FDPS mRNA sequence. The aminobisphosphonate drug includes zoledronic acid.
1. A viral vector comprising a therapeutic cargo portion, wherein the therapeutic cargo portion comprises:
a first small RNA sequence that is capable of binding to a first pre-determined complementary mRNA sequence, wherein the first pre-determined complementary mRNA sequence comprises a CD47 mRNA sequence,
wherein the first small RNA sequence comprises a sequence having at least about 80%, or at least about 85%, or at least about 90%, or at least about 95% identity with SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9; and
a second small RNA sequence that is capable of binding to a second pre-determined complementary mRNA sequence, wherein the second pre-determined complementary mRNA sequence comprises a cMyc mRNA sequence.
2. The viral vector of claim 1 , wherein the first small RNA sequence is under the control of a first promoter, and the second small RNA sequence is under the control of a second promoter.
3. The viral vector of claim 1 , wherein the first small RNA sequence and the second small RNA sequence are under the control of a single promoter.
4. The viral vector of claim 1 , wherein the small RNA sequences comprise a miRNA or a shRNA.
5. The viral vector of claim 1 , wherein the viral vector is a lentiviral vector.
6. The viral vector of claim 1 , wherein the first small RNA sequence comprises SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9.
7. A viral vector comprising a therapeutic cargo portion, wherein the therapeutic cargo portion comprises:
a first small RNA sequence that is capable of binding to a first pre-determined complementary mRNA sequence, wherein the first pre-determined complementary mRNA sequence comprises a CD47 mRNA sequence; and
a second small RNA sequence that is capable of binding to a second pre-determined complementary mRNA sequence, wherein the second pre-determined complementary mRNA sequence comprises a cMyc mRNA sequence,
wherein the second small RNA sequence comprises a sequence having at least about 80%, or at least about 85%, or at least about 90%, or at least about 95% identity with SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14.
8. The viral vector of claim 7 , wherein the second small RNA sequence comprises SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14.
9. A viral vector comprising a therapeutic cargo portion, wherein the therapeutic cargo portion comprises: a small RNA sequence that is capable of binding to a pre-determined complementary mRNA sequence, wherein the pre-determined complementary mRNA sequence comprises a CD47 mRNA sequence,
wherein the small RNA sequence comprises a sequence having at least about 80%, or at least about 85%, or at least about 90%, or at least about 95% identity with SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9.
10. The viral vector of claim 9 wherein the small RNA sequence comprises a miRNA or a shRNA.
11. The viral vector of claim 9 , wherein the viral vector is a lentiviral vector.
12. The viral vector of claim 9 , wherein the small RNA sequence comprises SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO: 9.
13. A method of treating cancer in a subject using an immunotherapy-based composition, the method comprising:
administering to the subject a therapeutically effective amount of a lentiviral particle comprising the viral vector of claim 1 .
14. The method of claim 13 , further comprising administering to the subject an effective amount of an aminobisphosphonate drug.
15. A method of treating cancer in a subject using an immunotherapy-based composition, the method comprising administering to the subject a therapeutically effective amount of a lentiviral particle comprising the viral vector of claim 9 .
16. The method of claim 15 , further comprising administering to the subject an effective amount of an aminobisphosphonate drug.
17. A method of treating cancer in a subject using an immunotherapy-based composition, the method comprising:
administering to the subject a therapeutically effective amount of a lentiviral particle comprising the viral vector of claim 7 .
18. A method of treating cancer in a subject using an immunotherapy-based composition, the method comprising:
(i) administering to the subject a therapeutically effective amount of a lentiviral particle comprising a viral vector comprising a therapeutic cargo portion, wherein the therapeutic cargo portion comprises:
a first small RNA sequence that is capable of binding to a first pre-determined complementary mRNA sequence, wherein the first pre-determined complementary mRNA sequence comprises a CD47 mRNA sequence; and
a second small RNA sequence that is capable of binding to a second pre-determined complementary mRNA sequence, wherein the second pre-determined complementary mRNA sequence comprises a cMyc mRNA sequence; and
(ii) administering to the subject an effective amount of an aminobisphosphonate drug.