This invention relates to modified T cells that inducibly express a bioactive molecule, such as IL-7, and constitutively expresses an antigen receptor, such as a T cell receptor or chimeric antigen receptor that binds to a tumour antigen. The modified T cells may comprise a nucleic acid construct that comprises a first nucleotide sequence encoding the bioactive molecule, a second nucleotide sequence encoding the antigen receptor; an inducible promoter operably linked to the first nucleotide sequence and a constitutive promoter operably linked to the second nucleotide. Nucleic acid constructs and vectors are provided, as well as T cells comprising such constructs and vectors and therapeutic methods and uses thereof.

Methods and compositions for treating cancers (e.g., neural cancers) by dendritic cell vaccination are provided herein.

Disclosed in the present application is a T cell receptor (TCR) capable of specifically recognizes MAGE-A4 antigenic peptide, including a TCR Polypeptide having at least 90% identity with any one selected from a group consisting of sequences of SEQ ID No: 1 to SEQ ID No: 30 and a TCR polypeptide having at least 90% identity with any one selected from a group consisting of sequences of SEQ ID No: 31 to SEQ ID No: 60, in which the TCR polypeptides are in one-to-one correspondence with the TCR polypeptides in order.

Provided herein are methods for delaying or inhibiting T cell maturation or differentiation in vitro for a T cell therapy, comprising contacting one or more T cells from a subject in need of a T cell therapy with an AKT inhibitor and at least one of exogenous Interleukin-7 (IL-7) and exogenous Interleukin-15 (IL-15), wherein the resulting T cells exhibit delayed maturation or differentiation. In some embodiments, the method further comprises administering the one or more T cells to a subject in need of a T cell therapy.

Provided is a dendritic cell therapeutic agent, and more particularly, a composition which include dendritic cells activated by peptides including a telomerase-derived peptide, the composition administered to treat an individual having disease and disorder symptoms which require target-specific treatments. Also, provided is a therapeutic method effective on diseases requiring target-specific immunotherapy. In the method, co-administration of the dendritic cell therapeutic agent and an immunotherapeutic agent including the telomerase-derived peptide results in decreased factors causing one of the disease and disorder symptoms requiring the target-specific treatment, such as cancer, in a tumor disease treatment.

The invention involves generating a T cell response to subdominant antigens and using the cells to therapeutically change the cellular homeostasis and nature of the immune response. In a preferred embodiment, the cells are generated outside of the patient avoiding the influence of the patient's immunologic milieu. By stimulating and growing the T cells from a patient in a tissue culture to one or more subdominant antigens and the transplanting them into the patient, if enough cells are expanded and transplanted, the transplanted cells overwhelm the endogenous dominant T cells in the response to either break or induce immune tolerance or otherwise modify the immune response to the cells or organism expressing that antigen. When the memory cells are established they are then reflective of this new immunodominance hierarchy so that the desired therapeutic effect is long lasting. In effect, the transplantation exogenously generated T cells reactive to the subdominant antigens is recapitulating priming and rebalancing the patient's immune response to target previously subdominant antigens in the cells or organism to produce a therapeutic benefit.

Disclosed is a method for enhancing the function of a T cell, which is characterized by inhibiting the expression of programmed death-1 ligand 1 (PD-L1) and/or programmed death-1 ligand 2 (PD-L2) in the T cell. Also disclosed is a function-enhanced T cell which is produced by the function enhancement method. Further disclosed is a therapeutic agent comprising the function-enhanced T cell. The T cell can enhance an immune response to cancer, and is useful in an immunotherapy effective for cancer and the treatment or prevention of infectious diseases and autoimmune diseases.

The present invention relates to an isolated T cell receptor (TCR) specific for a MAGEA1-derived peptide and to a polypeptide comprising a functional portion of the TCR. Further implicated are a multivalent TCR complex, a nucleic acid encoding a TCR, a cell expressing the TCR and a pharmaceutical composition comprising the TCR. The invention also refers to the TCR for use as a medicament, in particular to the TCR for use in the treatment of cancer.

The present disclosure provides methods for generating MAGE-B2 specific T cells and compositions comprising engineered MAGE-B2-specific T cell receptors. Further provided are methods of treating cancer comprising administering the MAGE-B2-specific T cells.

The present invention relates to a T cell comprising an engineered TCR-CD3 complex, wherein (a) binding of the engineered TCR-CD3 complex by a CD3 agonist results in a similar level of T cell activation compared to a T cell comprising a non-engineered TCR-CD3 complex; and (b) binding of the engineered TCR-CD3 complex by a cognate peptide-MHC complex results in a reduced level of T cell activation compared to a T cell comprising a non-engineered TCR-CD3 complex. Further encompassed are compositions comprising the T cell according to the invention and methods of uses thereof.