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.

Provided herein are methods of increasing T-cell function and T-cells produced by these methods. Also provided herein are methods of treating a subject using T-cells produced by these methods.

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 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.

The present invention relates to a method for ex vivo generating and expanding ?? Foxp3.sup.+ regulatory T cells, and therapeutic uses thereof. The inventors performed the induction of Foxp3? expression in ex vivo human induced tumor-antigen specific CD4+ TCR?? unrestricted T cells and the induction of autologous CD8-mediated T-cell responses against tumor-antigen specific FOXP3 expressing CD4+ TCR?? unrestricted T cells. The inventors developed a method to ex vivo generated and expanded antigen specific Foxp3 expressing CD3+ TCR?? unrestricted T cells, committed to exclusively exert regulatory activity, whichever culture condition of stimulation is. In particular, the present invention relates to a method for generating ex vivo ?? Foxp3+ regulatory T cells having the following phenotype: CD3+ TCR?? Foxp3+.

The present invention relates to a method for ex vivo generating and expanding MHCII restricted CD4.sup.+ Foxp3.sup.+ regulatory T cells, and therapeutic uses thereof. The inventors here demonstrated the optimal conditions for inducing Foxp3 expression in naive CD3+ CD4+ TCR??+ MHCII restricted T following polyclonal or following antigen-specific activation. They also developed an experimental procedure to generate autologous CD8+ T cell lines functionally committed to lyse tumor-antigen specific FOXP3 expressing TCR??+ MHCII restricted T cells, pathogenic CD4+ T cells that favour tumor cell immune evasion. In particular, the present invention relates to a method for generating ex vivo MHCII restricted CD4+ Foxp3+ regulatory T cells having the following phenotype: CD3+ CD4+ Foxp3+.

The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction of immune cells and are advantageously independent of the immune cell activation status. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Specifically, POU2AF1 modulation is provided for use as a marker, marker signature and molecular target. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from an increased immune response.

The present disclosure includes compositions and methods for treating gastrointestinal inflammatory disease and/or cancers. In certain aspects, the disclosure includes an isolated cell comprising a nucleic acid vector comprising a gene encoding the transcription factor ZBTB20 which is operably linked to a promoter.

Provided herein is a fusion protein comprising: (a) an extracellular domain comprising a first binding moiety that is capable of specifically binding to a first cell surface marker: (b) a transmembrane domain: and (c) an intracellular domain comprising: i. a first dimerization domain that specifically binds to a corresponding target dimerization domain in a target protein: and ii. a degradation domain, wherein the degradation domain is a degron or E3 ligase-recruiting domain. Protein circuits. cells and methods that make use of the fusion protein are also provided.

Provided herein are methods and compositions for the treatment of melanoma using anti-tumor immune cells treated with a PTD-MYC fusion protein (e.g., an HIV TAT-MYC fusion protein).