The University of Chicago

Massachusetts Institute of Technology

Helmholtz Zentrum Munchen Deutsches Forschungszentrum Fur Gesundheit Und Umwelt

Helmholtz Zentrum Munchen - Deutsches Forschungszentrum Fur Gesundheit U

Stefani Spranger

Thomas F Gajewski

Michael Leung

Dolores Schendel

Daniel Krappmann

Daniel Nagel

Ellen Duong

Provided herein are compositions and methods of use relating to a novel class of dendritic cells, referred to herein as ISG+ DC, having anti-tumor activity.

Compositions and methods for using cross-dressing to enhance anti-tumor immune responses

Provided herein are compositions and methods for the treatment of cancer by inhibition of β-catenin or a β-catenin pathway. In particular, inhibitors of β-catenin and/or the Wnt/β-catenin signaling pathway are employed prevent or reverse evasion of immune response or immunotherapy by cancers.

Beta-catenin inhibitors in cancer immunotherapy

The present disclosure provides combinations of immunologic inhibitors for the treatment of cancer. In some embodiments, the methods involve the use of a combination of at least two of the following: an inhibitor of indoleamine-2,3-dioxygenase (IDO), an inhibitor of the PD-L1/PD-1 pathway, an inhibitor of CTLA-4, an inhibitor of CD25, or IL-7.

Synergistic combination of immunologic inhibitors for the treatment of cancer

Provided herein are compositions and methods for the treatment of cancer by inhibition of &#x3b2;-catenin or a &#x3b2;-catenin pathway. In particular, inhibitors of &#x3b2;-catenin and/or the Wnt/p-catenin signaling pathway are employed prevent or reverse evasion of immune response or immunotherapy by cancers.

In some embodiments, the methods involve the use of a combination of at least two of the following: an inhibitor of indoleamine-2,3-dioxygenase (IDO), an inhibitor of the PD-L1/PD-1 pathway, an inhibitor of CTLA-4, an inhibitor of CD25, or IL-7. The inventors particularly observed a major synergistic effect of combining anti-CTLA-4 with either an IDO inhibitor, with anti-PD-L1 mAb, or with CD-25 depletion. Such combinations have been found to demonstrate a synergistic effect in treating cancer and tumors, for example by reducing tumor size, increasing the percentage of antigen-specific T cells, and increasing T cell function.

The invention relates to a compound for use in treating a cancer, wherein the cancer depends on the proteolytic activity of the MALT1 protease, and wherein the compound has the general formula (I) wherein X is N or C; Y is S, O, SO, SO, NH, CO, CH, CH&#x2550;CH, or CH&#x2014;CH; ( )is a C-Clinear or branched alkyl chain; A is NRR, or OR, or HET; Rand Rin each occurrence are independently selected from &#x2014;H, &#x2014;CH, &#x2014;OH, &#x2014;OCH, &#x2014;SCH, &#x2014;F, &#x2014;Cl, &#x2014;CF, &#x2014;NH, and &#x2014;COOH; R, R, and Rare H, or C-Clinear or branched alkyl groups, and HET is a heterocyclic ring of 5, 6, or 7 members, wherein the ring atoms can be C, O, N, or S, the ring can be saturated or aromatic, and the ring can be substituted with H or C-Clinear or branched alkyl groups; or a pharmaceutically acceptable salt, prodrug, enantiomer, diastereomer, racemic mixture, crystalline form, amorphous form, unsolvated form or solvate of said compound. The compound of the invention may further be used in the treatment of MALT1-dependent immune diseases.

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Chicago, IL, United States of America

Stefani Spranger