Inducible interleukin-12

1. An isolated or purified nucleic acid comprising a nucleotide sequence encoding a nuclear factor of activated T-cells (NFAT) promoter operatively associated with a nucleotide sequence encoding IL-12.

2. A nucleic acid comprising a nucleotide sequence encoding a nuclear factor of activated T-cells (NFAT) promoter operatively associated with a nucleotide sequence encoding IL-12, wherein the NFAT promoter is located 3′ of the nucleotide sequence encoding IL-12.

3. The nucleic acid of claim 1 , wherein the IL-12 is human IL-12.

4. The nucleic acid of claim 1 , wherein the IL-12 is single chain IL-12.

5. The nucleic acid of claim 1 , wherein the IL-12 comprises a sequence selected from the group consisting of SEQ NOs: 1-3.

6. The nucleic acid of claim 1 , wherein the NFAT promoter comprises SEQ ID NO: 4.

7. A nucleic acid comprising a nucleotide sequence that is complementary to the nucleic acid of claim 1 .

8. A nucleic acid comprising a nucleotide sequence that hybridizes to the nucleic acid of claim 1 at a temperature of 50-70° C. and an NaCl concentration of 0.02-0.1 M.

9. A recombinant expression vector comprising the nucleic acid of claim 1 .

10. A recombinant expression vector comprising the nucleic acid of claim 1 , wherein the recombinant expression vector comprises a sequence selected from the group consisting of SEQ NOs: 5-8, 11-12, and 14.

11. A recombinant expression vector comprising the nucleic acid of claim 2 , wherein the recombinant expression vector comprises a sequence selected from the group consisting of SEQ ID NOs: 7 and 14.

12. The recombinant expression vector of claim 9 , wherein the vector is selected from the group consisting of a retroviral vector, a lentiviral vector, a herpes viral vector, an adeno-associated viral vector, a transposon vector and an adenoviral vector.

13. A host cell comprising the recombinant expression vector of claim 9 .

14. The host cell of claim 13 , further comprising a recombinant expression vector comprising a nucleotide sequence encoding a T cell receptor (TCR).

15. The host cell of claim 14 , wherein the TCR has antigenic specificity for an infectious disease antigen.

16. The host cell of claim 15 , wherein the infectious disease antigen is selected from the group consisting of an HIV antigen, an influenza antigen, a Herpes virus antigen, a hepatitis antigen, and a malaria antigen.

17. The host cell of claim 14 , wherein the TCR has antigenic specificity for a cancer antigen.

18. The host cell of claim 17 , wherein the cancer antigen is a melanoma antigen.

19. The host cell of claim 17 , wherein the cancer antigen is selected from the group consisting of p53, RB, Her2/neu, CEA, PSMA, NY-ESO-1, MAGE, gp100, TRP-1, MART-1, tyrosinase tumor antigen, PSCA, HMW-MAA, CD19, VEGFR2, SSX, and EGFRvIII.

20. The host cell of claim 19 , wherein the nucleotide sequence encoding the TCR is selected from the group consisting of SEQ ID NO: 9, SEQ ID NO: 10, and SEQ ID NO: 13.

21. A population of cells comprising at least one host cell of claim 13 .

22. A pharmaceutical composition comprising the nucleic acid of claim 1 and a pharmaceutically acceptable carrier.

23. A method of treating a mammal with a cancer or an infectious disease, wherein the mammal expresses a cancer antigen or an infectious disease antigen, the method comprising:

(a) isolating autologous T cells from the mammal, wherein the T cell expresses a T cell receptor (TCR) specific for the cancer antigen or the infectious disease antigen;

(b) transducing the T cells with the recombinant expression vector of claim 9 ; and

(c) administering the T cells of (b) to the mammal, wherein upon administering the T cells to the mammal, the cancer antigen or the infectious disease antigen stimulates expression of the nucleotide sequence encoding IL-12 and treats the mammal with the cancer or infectious disease.

24. A method of inducing IL-12 expression in a mammal expressing an antigen, the method comprising:

a) isolating autologous T cells from a mammal;

b) transducing the isolated T cells with the recombinant expression vector of claim 9 ;

c) transducing the isolated T cells with a second recombinant expression vector comprising a nucleotide sequence encoding a TCR specific for the antigen, wherein the nucleotide sequence encoding the TCR is operably linked to a promoter;

d) administering the transduced cells to the mammal; and

e) stimulating the TCR by the antigen, wherein the transduced T cell expresses the TCR specific for the antigen and the stimulating induces IL-12 expression.

25. A method of treating a mammal with a cancer or an infectious disease, the method comprising:

a) isolating autologous T cells from the mammal, wherein the T cell expresses a T cell receptor (TCR) specific for an antigen;

b) transducing the T cells with the recombinant expression vector of claim 9 ;

c) administering the T cells of b) to the mammal; and

d) administering the antigen to the mammal, wherein upon administering the antigen to the mammal, the antigen stimulates expression of the nucleotide sequence encoding IL-12 and treats the mammal with the cancer or the infectious disease.

26. A method of inducing IL-12 expression in a mammal, the method comprising:

a) isolating autologous T cells from a mammal;

b) transducing the isolated T cells with the recombinant expression vector of claim 9 ;

c) transducing the isolated T cells with a second recombinant expression vector comprising a nucleotide sequence encoding a TCR specific for an antigen, wherein the nucleotide sequence encoding the TCR is operably linked to a promoter;

d) administering the transduced T cells to the mammal; and

e) stimulating the TCR by administering the antigen, wherein the transduced T cell expresses the TCR specific for the antigen and the stimulating induces IL-12 expression.