Compositions and methods for increasing mesenchymal stromal cell migration to tumors

Patent metadata

Field	Value
Publication number	US-11173180-B2
Application number	US-201815892680-A
Country	US
Kind code	B2
Filing date	Feb 9, 2018
Priority date	Sep 6, 2013
Publication date	Nov 16, 2021
Grant date	Nov 16, 2021

Abstract

The present application is directed to compositions and methods for treating a subject with cancer and/or increasing migration of a mesenchymal stromal cells (MSCs) stimulated with a recombinant autocrine motility factor (rAMF) to a tumor or a tumor cell, e.g. hepatocellular carcinoma (HCC). In addition, methods for increasing adhesion of MSCs to endothelial cells with rAMF are disclosed. In some embodiments, the MSCs comprise a therapeutic agent, e.g., an anti-tumor agent.

First claim

What is claimed is:

1. A method for increasing migration or anchorage of a mesenchymal stromal cell (MSC) to a tumor comprising
(a) stimulating the MSC by in vitro pretreatment with a recombinant autocrine motility factor (rAMF) of SEQ ID NO:1, wherein the rAMF is capable of increasing migration or anchorage of a stimulated MSC, and
(b) administering the stimulated MSC of (a) to the tumor, wherein the MSC comprises a recombinant therapeutic agent,
wherein the vitro pretreatment comprises incubating the MSC with a medium comprising the rAMF followed by removal of the medium containing the rAMF.

2. A method for treating a subject with a tumor comprising
(a) stimulating a mesenchymal stromal cell (MSC) comprising a recombinant therapeutic agent by in vitro pretreatment with a recombinant autocrine motility factor (rAMF) of SEQ ID NO:1, wherein the rAMF is capable of increasing migration or anchorage of a stimulated MSC, and
(b) administering the stimulated MSC of (a) to the subject,
wherein the in vitro pretreatment comprises incubating the MSC with a medium comprising the rAMF followed by removal of the medium containing the rAMF.

3. The method of claim 1 , wherein the tumor is a solid tumor.

4. The method of claim 1 , wherein the tumor is a cancer selected from the group consisting of a liver cancer, a colon cancer, a pancreatic cancer, a lung cancer, a gastrointestinal cancer, a kidney cancer, or a breast cancer.

5. The method of claim 1 , wherein the tumor is a carcinoma.

6. The method of claim 5 , wherein the carcinoma is hepatocellular carcinoma (HCC).

7. The method of claim 5 , wherein the carcinoma is colorectal carcinoma.

8. The method of claim 1 , wherein the tumor expresses endogenous AMF.

9. The method of claim 1 , wherein the increasing migration is two-fold greater than migration of the MSC without rAMF stimulation.

10. The method of claim 1 , wherein the source of the MSC is selected from the group consisting of bone marrow, adipose tissue, and umbilical cord.

11. The method of claim 10 , wherein the umbilical cord MSC is harvested from human umbilical cord perivascular tissue.

12. The method of claim 1 , wherein the recombinant therapeutic agent is a recombinant anti-tumor gene.

13. The method of claim 1 , wherein the recombinant therapeutic agent is an oncolytic virus.

14. The method of claim 13 , wherein the oncolytic virus is engineered to express a recombinant anti-tumor gene.

15. The method of claim 12 , wherein the recombinant anti-tumor gene is selected from the group consisting of an interferon, an interleukin, a chemokine, a suicide gene, and any combination thereof.

16. The method of claim 15 , wherein the anti-tumor gene is selected from the group consisting of interferon α, interferon ρ, interleukin 1, interleukin 12, CX3CL1, thymidine kinase, IL-12, IFN-gamma, TNF-alpha, or any combination thereof.

17. The method of claim 1 , wherein the MSC further comprises a recombinant AMF receptor.

18. The method of claim 2 , wherein the administration is systemic.

19. The method of claim 2 , wherein the administration is to an intra-hepatic artery.

Assignees

• Consejo Nacional De Investigaciones Cientificas Y Tecn Conicet
• Asoc Civil De Estudios Superiores
• Inis Biotech Llc
• Consejo National De Investigaciones Cientificas Y Tecn Conicet

Inventors

• Mazzolini Guillermo Daniel
• Garcia Mariana Gabriela
• Bayo Juan

Classifications

• C12N5/0668 Primary

  Mesenchymal stem cells from other natural sources · CPC title

• C12N2501/998

  Proteins not provided for elsewhere · CPC title

• C12N2501/40

  Regulators of development · CPC title

• C12N2502/99

  genetically modified cells · CPC title

• C12N2501/20

  Cytokines; Chemokines · CPC title