Somatostatin receptor-based cancer therapy
AssigneeBoard of Regents, The University of Texas System
InventorVikas KUNDRA
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Abstract
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.
Claims84
A method of treating a tumor, comprising the steps of:
- a) providing 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;
- b) introducing the cells to a subject having a tumor;
- and
- c) administering to the subject an anti-tumor therapeutic that specifically binds the somatostatin receptor and effects a damage on the tumor.
The method of any of preceding claims, wherein the cells are stem cells, progeny cells thereof, immune cells, or fibroblast cells.
The method of any of preceding claims, wherein the somatostatin receptor is a SSTR2 mutant.
The method of any of preceding claims, wherein the somatostatin receptor is a mutant of a human somatostatin receptor.
The method of any of preceding claims, wherein the somatostatin receptor has a C-terminal deletion.
The method of any of preceding claims, wherein the somatostatin receptor has a C-terminal deletion of an amino acid sequence with at least about 90% homology to a C terminal 55-amino acid sequence of human SSTR2 (i.e., amino acid positions 315-369 of SEQ ID NO:6) as compared with a corresponding native somatostatin receptor.
The method of any of preceding claims, wherein the somatostatin receptor is human SSTR2 delta 314 mutant with the sequence of amino acid 1-314 of SEQ ID NO:6.
The method of any of preceding claims, wherein the expression construct further comprises a second coding sequence.
The method of any of preceding claims, wherein the tumor is neuroendocrine tumor, breast tumor, lung tumor, prostate tumor, ovarian tumor, brain tumor, liver tumor, cervical tumor, colon tumor, renal tumor, skin tumor, head and neck tumor, bone tumor, esophageal tumor, bladder tumor, uterine tumor, lymphatic tumor, stomach tumor, pancreatic tumor, testicular tumor, or lymphoma.
The method of any of preceding claims, wherein the therapeutic comprises a therapeutic radionuclide.
The method of any of preceding claims, wherein the therapeutic is coupled to a ligand that specifically binds the somatostatin receptor.
The method of any of preceding claims, further comprising tracking the cells or expression of the expression construct in the subject.
The method of any of preceding claims, further comprising imaging the cells.
The method of any of preceding claims, further comprising administering to the subject a detectable moiety coupled to a ligand that specifically binds the somatostatin receptor.
The method of any of preceding claims, further comprising imaging the cells via MRI, MR spectroscopy, radiography, CT, ultrasound, planar gamma camera imaging, SPECT, PET, nuclear medicine-based imaging, optical imaging using visible light, optical imaging using luciferase, optical imaging using a fluorophore, optical imaging, imaging using near infrared light, imaging using infrared light, photoacoustic imaging or thermoacoustic imaging.
A method of treating a tumor, comprising the steps of:
- a) providing cells comprising stem cells, progeny cells thereof, fibroblasts, wherein the cells are capable of localizing to a tumor;
- b) introducing the cells to a subject having a tumor;
- and
- c) administering to the subject an anti-tumor radiotherapeutic or thermal therapeutic that binds the cells and effects a damage on the tumor.
A constitutively active somatostatin receptor type 2 mutant.
A composition comprising cells capable of localizing to a tumor for use in the treatment of a subject having 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, wherein the cells are to be administered to the subject prior to administering to the subject an anti-tumor therapeutic that specifically binds the somatostatin receptor and effects a damage on the tumor.
The composition of any of 43-48, wherein the somatostatin receptor is a SSTR2 mutant.
A composition comprising cells capable of localizing to a tumor for use in the treating of a tumor, wherein the cells comprise stem cells, progeny cells thereof, fibroblasts, wherein the cells are to be administered to the subject prior to administering to the subject an anti-tumor therapeutic radionuclide or thermal therapeutic that specifically binds the cells and effects a damage on the tumor.
A constitutively active somatostatin receptor type 2 mutant.
Dependencies are inferred from the claim text.