Somatostatin receptor-based cancer therapy
Methods and composition for cell-based therapy as well as somatostatin receptor-based therapy are described. For example, in certain aspects methods for administering an anti-tumor therapy using a signaling defective somatostatin receptor mutant are described. Furthermore, the invention provides compositions and methods involve a somatostatin constitutively active somatostatin receptor mutant.
1. A composition comprising stem cells or immune cells capable of localizing to a tumor, wherein the cells comprise an exogenous expression construct having a nucleic acid sequence encoding a somatostatin receptor, wherein the somatostatin receptor is a native somatostatin receptor or a mutant thereof, further wherein, in the case of stem cells, the stem cells are induced pluripotent stem cells, mesenchymal stem cells, embryonic stem cells, somatic stem cells, germ stem cells, epidermal stem cells or tissue-specific stem cells.
2. The composition of claim 1 , wherein the somatostatin receptor is a native somatostatin receptor.
3. The composition of claim 1 , wherein the somatostatin receptor is a signaling defective somatostatin receptor.
4. The composition of claim 1 , wherein the somatostatin receptor is a constitutively active receptor.
5. The composition of claim 1 , wherein the somatostatin receptor has at least trans-membrane domains III-VII of a native somatostatin receptor.
6. The composition of claim 1 , wherein the somatostatin receptor is a SSTR2 mutant.
7. The composition of claim 1 , wherein the somatostatin receptor has a C-terminal deletion.
8. The composition of claim 1 , wherein the somatostatin receptor is human SSTR2 delta 314 mutant with the sequence of amino acid 1-314 of SEQ ID NO:6.
9. The composition of claim 1 , wherein the somatostatin receptor is human SSTR2 delta 340 mutant with the sequence of amino acid 1-340 of SEQ ID NO:6.
10. The composition of claim 1 , wherein the expression construct further comprises a second coding sequence, wherein the second coding sequence is a protein tag gene, reporter gene, a therapeutic gene, a signaling sequence, or a trafficking sequence.
11. The composition of claim 1 , wherein the immune cells are T cells, B cells, lymphocytes, NK cells, white blood cells, or immune progenitor cells.
12. The composition of claim 1 , wherein the cells are cells engineered to localize to a tumor.
13. The composition of claim 1 , wherein the cells are cells engineered to localize to a tumor expressing an antigen or chemoattractant.
14. A composition comprising stem cells, immune cells or fibroblast cells capable of localizing to a tumor, wherein the cells comprise an exogenous expression construct having a nucleic acid sequence encoding a constitutively active somatostatin receptor mutant.
15. The composition of claim 14 , wherein the somatostatin receptor mutant has at least trans-membrane domains III-VII of a native somatostatin receptor.
16. The composition of claim 14 , wherein the somatostatin receptor is a SSTR2 mutant.
17. The composition of claim 14 , wherein the somatostatin receptor has a C-terminal deletion.
18. The composition of claim 14 , wherein the somatostatin receptor is human SSTR2 delta 314 mutant with the sequence of amino acid 1-314 of SEQ ID NO:6.
19. The composition of claim 14 , wherein the somatostatin receptor is human SSTR2 delta 340 mutant with the sequence of amino acid 1-340 of SEQ ID NO:6.
20. The composition of claim 14 , wherein the expression construct further comprises a second coding sequence, wherein the second coding sequence is a protein tag gene, reporter gene, a therapeutic gene, a signaling sequence, or a trafficking sequence.
21. The composition of claim 14 , wherein the cells are stem cells.
22. The composition of claim 21 , wherein the stem cells are induced pluripotent stem cells, mesenchymal stem cells, embryonic stem cells, somatic stem cells, germ stem cells, epidermal stem cells, and/or tissue-specific stem cells.
23. The composition of claim 14 , wherein the cells are immune cells.
24. The composition of claim 23 , wherein the immune cells are T cells, B cells, lymphocytes, NK cells, white blood cells, or immune progenitor cells.
25. The composition of claim 14 , wherein the cells are cells engineered to localize to a tumor.
26. The composition of claim 14 , wherein the cells are cells engineered to localize to a tumor expressing an antigen or chemoattractant.