Methods for cancer treatment

Patent metadata

Field	Value
Publication number	US-10549082-B2
Application number	US-201414783997-A
Country	US
Kind code	B2
Filing date	Apr 17, 2014
Priority date	Apr 17, 2013
Publication date	Feb 4, 2020
Grant date	Feb 4, 2020

Abstract

Residual, refractory or relapsed cancer is treated by immunostimulation in the presence of allogeneic immune effector cells, optimally in combination with radiation therapy. The methods of the disclosure induce a systemic allogeneic anti-tumor immune response that results in tumor regression in untreated sites of disease, i.e. non-injected, non-irradiated, etc.

First claim

What is claimed is:

1. A method of treating a cancer in a subject, the method comprising intratumorally administering into a tumor in the subject that has undergone an allogenic hematopoietic stem cell transplantation an immunostimulant while concurrently providing local field irradiation of the tumor in the subject's body, wherein a combination of the immunostimulant and the local field irradiation induces allogeneic immune cells to generate an anti-tumor response to HLA alloantigens expressed by the tumor, causing a systemic allogeneic anti-tumor T-cell immune response that results in tumor regression in a second, untreated site of disease in the subject's body, and wherein the method is conducted without use of a chemotherapeutic agent.

2. The method of claim 1 , wherein said allogeneic anti-tumor T cell immune response further comprises at least about 5% circulating allogeneic type CD3 + T cells.

3. The method of claim 1 , wherein said subject has at least about 5% allogeneic type leukocytes.

4. The method of claim 1 , wherein said irradiation is an irradiation at a tumor nodule.

5. The method of claim 1 , wherein said irradiation is selected from the group consisting of ionizing radiation, thermal therapy, ultrasound, irreversible electroporation (IRE), oxidative stress, radiofrequency ablation and combinations thereof.

6. The method of claim 1 , wherein said immunostimulant is an oligodeoxynucleotide (ODN), said ODN further comprises a CpG that binds to a Toll-Like Receptor (TLR) 9 so as to activate dendritic cells and B-cells.

7. The method of claim 1 , wherein said cancer is a solid tumor or a lymphoma.

8. The method of claim 7 , wherein said cancer is a lymphoma, said lymphoma is selected from the group consisting of a Non-Hodgkin's lymphoma, a Hodgkin's lymphoma, a cutaneous T-cell lymphoma and a mycosis fungoides.

9. The method of claim 1 , wherein said cancer is a renal cell carcinoma.

10. The method of claim 1 , wherein said cancer is selected from the group consisting of a residual cancer, a relapsed cancer and a refractory cancer.

11. The method of claim 1 , wherein said second, untreated site of disease further comprises a tumor that has not been injected with said immunostimulant.

Assignees

• Univ Leland Stanford Junior

Inventors

• Lowsky Robert
• Engleman Edgar George
• Strober Samuel

Classifications

• A61N5/10

  X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence) · CPC title

• A01K2207/35

  Animals modified by environmental factors, e.g. temperature, O2 · CPC title

• C12N15/117

  Nucleic acids having immunomodulatory properties, e.g. containing CpG-motifs · CPC title

• A61B18/08

  by means of electrically-heated probes · CPC title

• C12N2320/31

  Combination therapy · CPC title