Treatment and bioluminescent visualization using multimodal TRAIL molecules
Described herein are novel compositions comprising multimodal TRAIL agents and cells engineered to express such multimodal TRAIL agents, including cells encapsulated in a scaffold or matrix, for use in the treatment of disorders such as cancer.
1. A method of treatment and bioluminescent visualization for a subject having a malignant condition comprising administering a therapeutically effective amount of a pharmaceutical composition comprising a soluble TRAIL fusion protein comprising, in the following N-terminal to C-terminal order, a reporter module, a linker module of at least 8 amino acids, and a therapeutic TRAIL module, wherein said therapeutic TRAIL module comprises an extracellular domain of human TRAIL of SEQ ID NO: 1, and a pharmaceutically acceptable carrier.
2. The method of claim 1 , wherein the malignant condition is a glioblastoma.
3. The method of claim 1 , further comprising administering to the subject, one or more additional chemotherapeutic agents, biologics, drugs, or treatments as part of a combinatorial therapy.
4. The method of claim 3 , wherein the chemotherapeutic agent, biologic, drug, or treatment is selected from the group consisting of: radiation therapy, tumor resection surgery, gemcitabine, cisplastin, paclitaxel, carboplatin, bortezomib, AMG479, vorinostat, rituximab, temozolomide, rapamycin, ABT-737, and PI-103.
5. The method of claim 1 , wherein the pharmaceutical composition is administered at a surgical site.
6. The method of claim 5 , wherein the surgical site is a tumor resection site.
7. The method of claim 1 , wherein the linker domain comprises the amino acid sequence of SEQ ID NO: 4.
8. The method of claim 1 , wherein the therapeutic TRAIL module comprises amino acids 39-281 of SEQ ID NO: 1.
9. The method of claim 1 , wherein the therapeutic TRAIL module comprises amino acids 95-281 of SEQ ID NO: 1.
10. The method of claim 1 , wherein the therapeutic TRAIL module comprises amino acids 114-281 of SEQ ID NO: 1.
11. The method of claim 1 , wherein the therapeutic TRAIL module consists of amino acids 114-281 of SEQ ID NO: 1.
12. The method of claim 1 , wherein the soluble TRAIL fusion protein is encoded by a human stem cell comprising a nucleic acid sequence encoding the soluble TRAIL agent.
13. The method of claim 12 , wherein the human stem cell is encapsulated in a matrix or scaffold.