Massachusetts Institute of Technology

The General Hospital Corporation

Dana-Farber-Cancer Institute Inc.

The Broad Institute, Inc.

Mario Suva

Aviv Regev

Itay Tirosh

Kai W Wucherpfennig

Bradley Bernstein

Nathan D Mathewson

Volker Hovestadt

Mariella Filbin

The subject matter disclosed herein is generally directed to compositions and methods for treating diffuse gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-gliomas). Disclosed herein are gene signatures specific for tumor cell types and compositions for treatment of H3K27M gliomas. In one embodiment, PRC1 is targeted in a treatment regimen for H3K27M-gliomas.

Methods and compositions for targeting developmental and oncogenic programs in H3K27M gliomas

Provided are methods and compositions for treating cancer in a subject in need thereof. One of the top gene products in glioblastoma multiforme (GBM) is KLRB1 (also known as CD161), a C-type lectin protein that binds to CLEC2D. Binding of CLEC2D to the KLRB1 receptor inhibits the cytotoxic function of NK cells as well as cytokine secretion. KLRB1 is only expressed by small subpopulations of human blood T cells, and consequently little is known about the function of this receptor in T cells. However, preliminary data demonstrate that KLRB1 expression is induced in T cells within the GBM microenvironment. In an exemplary embodiment, a method is provided comprising administering an agent capable of blocking the interaction of KLRB1 with its ligand. The agent may comprise an antibody or fragment thereof, which may bind KLRB1 or CLEC2D.

Methods and compositions for treating cancer by targeting the CLEC2D-KLRB1 pathway

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Boston, MA, United States of America

Mario Suva