Claims for Patent: 10,016,421

Summary for Patent: 10,016,421

Title:	Histone deacetylase 6 inhibition for enhancing T-cell function during anti-tumor response and tumor-peptide vaccination
Abstract:	Disclosed are methods whereby an effective amount of a HDAC6 inhibitor is used to activate a subjects T-cell response to tumor or tumor vaccine. Methods of using HDAC6 inhibitors to increase a subjects anti-tumor immune response, alone or in conjunction with other tumor treatments, are also disclosed.
Inventor(s):	Sotomayor; Eduardo M. (Tampa, FL), Villagra; Alejandro V. (Tampa, FL)
Assignee:	H. Lee Moffitt Cancer Center and Research Institute, Inc. (Tampa, FL)
Application Number:	15/120,053
Patent Claims:	1. A method of increasing expression of CD69 in a subject's T-cells, comprising: administering to a subject having melanoma, ovarian cancer, breast cancer, or colorectal cancer an amount of a HDAC6 inhibitor effective to increase expression of CD69 in the subject's T-cells, wherein the HDAC6 inhibitor is selected from the group consisting of ACY1215, Tubstatin A, Tubacin, and any combination thereof. 2. The method of claim 1, wherein the inhibitor is ACY1215. 3. The method of claim 1, wherein the inhibitor is Tubstatin A, Tubacin, or any combination thereof. 4. The method of claim 1, wherein the subject is also administered ipilimumab, revlimid, velcade, vemurafenib, or any combination thereof. 5. A method for ex vivo expanding tumor-infiltrating lymphocytes for use in adoptive cell therapy, comprising: culturing tumor fragments from the subject in a culture medium comprising IL-2 and an HDAC6 inhibitor selected from the group consisting of ACY1215, Tubstatin A, Tubacin, and any combination thereof in an amount effective to expand tumor-infiltrating lymphocytes with enriched tumor-reactivity and specificity. 6. A method for treating melanoma, ovarian cancer, breast cancer, or colorectal cancer in a subject, comprising: expanding tumor-infiltrating lymphocytes from a tumor fragment from the subject by culturing the tumor fragments in a culture medium comprising IL-2 and an HDAC6 inhibitor selected from the group consisting of ACY1215, Tubstatin A, Tubacin, and any combination thereof in an amount effective to expand tumor-infiltrating lymphocytes with enriched tumor-reactivity and specificity; treating the subject with nonmyeloablative lymphodepleting chemotherapy; and administering the tumor-infiltrating lymphocytes to the subject. 7. The method of claim 1, wherein the oncological disorder is metastatic. 8. The method of claim 1, wherein the oncological disorder is recurrent. 9. The method of claim 1, wherein the subject is a human. 10. The method of claim 6, wherein the inhibitor is ACY1215. 11. The method of claim 6, wherein the inhibitor is Tubstatin A, Tubacin, or any combination thereof. 12. A method of increasing T-cell activation and response against peptide vaccine, comprising: administering to a subject an effective amount of an HDAC6 inhibitor selected from the group consisting of ACY1215, Tubstatin A, Tubacin, and any combination thereof to increase T-cell activation and response against tumor or peptide vaccine in the subject. 13. The method of claim 12, wherein the HDAC6 inhibitor is administered with the peptide vaccine. 14. The method of claim 12, wherein the HDAC6 inhibitor is administered within a week after the subject has been administered a peptide vaccine.

Details for Patent 10,016,421

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Bristol-myers Squibb Company	YERVOY	ipilimumab	Injection	125377	03/25/2011		2034-04-05