H. Lee Moffitt Cancer Center and Research Institute, Inc.

University of Illinois

University of South Florida

Dana-farber-cancer Institute Inc.

Eduardo M Sotomayor

Alejandro V Villagra

Alan P Kozikowski

Karrune Veeraprasert Woan

Joel Bergman

James Elliott Bradner

Jianguo Tao

Ildefonso Suarez

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.

Histone deacetylase 6 inhibition for enhancing T-cell function during anti-tumor response and tumor-peptide vaccination

Inhibition of bromodomain proteins in antigen presenting cells is shown herein to be more inflammatory, to display lower expression of the immunosuppressive molecule PDL1, and to be capable of restoring the responsiveness of tolerant T-cells. Therefore, disclosed is a method for promoting T-cell activation during cancer immunotherapy in a subject that involves administering to a subject undergoing cancer immunotherapy a composition comprising a bromodomain inhibitor. Also disclosed is a method for treating cancer in a subject, comprising co-administering to the subject a bromodomain inhibitor and an immunostimulatory agent.

Bromodomain inhibitor as adjuvant in cancer immunotherapy

Disclosed herein is a method for modulating Program Death Receptor Ligand 1 (PDL1) in a cancer cell, comprising contacting the cell with a composition comprising a histone deacetylase (HDAC) inhibitor. Also disclosed is a method for treating a tumor in a subject, comprising administering to the subject a therapeutically effective amount of a composition comprising a histone deacetylase (HDAC) inhibitor and a composition comprising a therapeutically effective amount of a Program Death Receptor Ligand 1 (PDL1) inhibitor, a Programmed Death 1 receptor (PD1) inhibitor, or a combination thereof.

Histone deacetylase as a modulator of PDLI expression and activity

Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula I. Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed.

Selective histone deactylase 6 inhibitors

Histone deacetylase as a modulator of PDL1 expression and activity

Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula (I). Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed. 

Disclosed are selective histone deactylase inhibitors (HDACi) that having Formula I. Specifically, the disclosed subject matter relates to compounds having activity as selective HDAC6 inhibitors, methods of making and using the compounds, and compositions comprising the compounds. In still further aspects, the disclosed subject matter relates to methods for treating oncological disorders in a patient. Methods of making and using these inhibitors for the treatment of cancer, in particular melanoma are also disclosed.

The present invention provides adjuvants, vaccines and related methods that are useful in eliciting immune responses, particularly immune responses against tumor antigens. We discovered that flagellin is capable of inhibiting tolerance when it is administered in conjunction with a tolerogenic antigen. This effect is likely mediated by the ability of flagellin to induce IL-12 while keeping IL-10 levels low. Furthermore, flagellin can be provided in an extended-releasing manner by using a flagellin-expressing cell. Preferably, the flagellin-expressing cell is treated such that it is no longer capable of replicating, yet retaining the ability to express flagellin, such as by lethal irradiation.

Growing community of inventors

Tampa, FL, United States of America

Eduardo M Sotomayor