Compositions and methods of selectively activating Akt3 are provided.

The present disclosure provides modified immune cells or precursors thereof comprising disrupted Fli1. Compositions and methods of treatment are also provided. The disclosure also provides methods for screening T cells, including assessing T cell exhaustion.

Methods to treat cancer in a subject comprising administering to the subject a therapeutically effective amount of T-cells of the subject having increased IRF4 polypeptide expression compared to a control are disclosed. Also disclosed are methods of increasing tumor reactivity of a T-cell by increasing IRF4 polypeptide expression, and methods to predict the likelihood that a subject having cancer will respond therapeutically to administered T-cells having increased IRF4 polypeptide expression. Also disclosed are compositions comprising a T-cell and a viral vector encoding an IRF4 polypeptide. The compositions are methods are useful for treating numerous cancers in which higher level expression of IRF4 in T-cells would be beneficial. In some embodiments, activated tumor-specific T-cells having increased IRF4 expression have greater infiltration in tumors and enhanced local immunological responses.

Disclosed herein are chimeric antigen receptor effector cells (CAR-ECs) and CAR-EC switches. The switchable CAR-ECs are generally T cells. The one or more chimeric antigen receptors may recognize a peptidic antigen on the CAR-EC switch. The CAR-ECs and switches may be used for the treatment of a condition in a subject in need thereof.

The present invention provides a complex for use in the prevention and/or treatment of cancer, the complex comprising a) a cell penetrating peptide, b) at least one antigen or antigenic epitope, and c) at least one TLR peptide agonist, wherein the components a)-c) are covalently linked. In particular, compositions for use in the prevention and/or treatment of cancer, such as a pharmaceutical compositions and vaccines are provided.

Disclosed herein are chimeric antigen receptor effector cells (CAR-ECs) and CAR-EC switches. The switchable CAR-ECs are generally T cells. The one or more chimeric antigen receptors may recognize a peptidic antigen on the CAR-EC switch. The CAR-ECs and switches may be used for the treatment of a condition in a subject in need thereof.

This disclosure provides a method of identifying or separating activated regulatory T cells that have a demethylated Foxp3 TSDR region from a mixture of activated T cells. The mixture is depleted of cells bearing the CD154 molecule (CD40 ligand). The desired cells can be recovered using a Treg marker such as CD25, GITR, CTLA4, CD137, latent TGF-beta (LAP), GARP (LRRC32) or CD121a/b. The Treg cells having a demethylated Foxp3 TSDR region can be used, for example for preparation of pharmaceutical compositions for use in treatment.

This document provides methods and materials for treating cancer. For example, methods and materials for identifying antigens and combinations of antigens that can be used to treat cancer as well as combinations of antigens having the ability to reduce established tumors (e.g., gliomas) within a mammal (e.g., a human) are provided. In general, one aspect of this document features a composition comprising, or consisting essentially of, nucleic acid encoding HIF-2a, SOX-10, C-MYC, and TYRP-1, wherein the composition comprises less than 100 separate nucleic acid molecules.

The present invention relates to semi-allogeneic antigen-presenting cells into which proteins and/or peptides or RNA or DNA or cDNA, respectively, encoding said proteins and/or peptides which are overexpressed in tumor cells or which are derived from autologous tumor cells or different tumor cells or different tumor cell lines have been introduced. Furthermore the invention relates to methods for the generation of these semi-allogeneic antigen-presenting cells as well as to the use thereof in the treatment of tumor diseases.

Methods, compositions and kits for producing functional antigen-specific regulatory T cells (Tr1 cells) by reprogramming non-Tr1 target cells with suitable transcription factors.