PD-1 antagonists are disclosed that can be used to reduce the expression or activity of PD-1 in a subject. An immune response specific to an infectious agent or to tumor cells can be enhanced using these PD-1 antagonists in conjunction with an antigen from the infectious agent or tumor. Thus, subjects with infections, such as persistent infections can be treated using PD-1 antagonists. In addition, subjects with tumors can be treated using the PD-1 antagonists. In several examples, subjects can be treated by transplanting a therapeutically effective amount of activated T cells that recognize an antigen of interest and by administering a therapeutically effective amount of a PD-1 antagonist.

Provided are compositions for use in methods for treating diseases associated with expression of mesothelin comprising administering a cell that expresses a chimeric antigen receptor (CAR) specific to mesothelin in combination with a PD-L1 inhibitor.

The present invention relates to the combination of a T cell receptor (TCR) specific for the FRAME peptide SLLQH-LIGL and a chimeric co-stimulatory receptor comprising an extracellular domain derived from PD-1(CD279) and an intracellular domain derived from 4-1BB (CD137). In particular, the invention refers to a cell comprising said TCR and chimeric co-stimulatory protein. Further the invention refers to a nucleic acid encoding the TCR and the co-stimulatory receptor, a corresponding vector and a corresponding nucleic acid composition. Moreover, the invention relates to the according pharmaceutical composition. Accordingly the invention also relates to the cell and the nucleic acid constructs for use as a medicament, in particular to the TCR for use in the treatment of cancer.

The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR ? chain, TCR ? chain, beta-2 microglobulin, a HLA molecule, CTLA-4, PD1, and FAS and further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

Provided are combination therapies for treating and preventing relapse of a tumor and infectious diseases in a subject, as well as methods for use thereof. The combination therapies comprise an Hsp70 based pharmaceutical ingredient and at least one further immunotherapeutic agent that specifically inhibits and/or preferably binds to an immune checkpoint molecule or tumor immune microenvironment immune regulator. Furthermore, a kit and methods of using the combination therapies of the invention are described.

The present disclosure provides systems for immune cell regulation and methods of immunotherapy. Systems of the present disclosure for immune cell regulation comprise a chimeric receptor polypeptide, a chimeric adaptor polypeptide, a gene modulating polypeptide (GMP), and a cleavage moiety.

The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR ? chain, TCR ? chain, beta-2 microglobulin and FAS further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

The present invention relates to methods for developing engineered immune cells such as T-cells for immunotherapy that have a higher potential of persistence and/or engraftment in host organism. IN particular, this method involves an inactivation of at least one gene involved in self/non self recognition, combined with a step of contact with at least one non-endogenous immunosuppressive polypeptide. The invention allows the possibility for a standard and affordable adoptive immunotherapy, whereby the risk of GvH is reduced.

The present disclosure provides improved genome editing compositions and methods for editing a PD-1 gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of, a cancer, an infectious disease, an autoimmune disease, an inflammatory disease, or an immunodeficiency.

The invention is based on the disclosure provided herein that secondary lymphoid organ chemokine (SLC) inhibits the growth of syngeneic tumors in vivo. Thus, the invention provides a method of treating cancer in a mammal subject by administering a therapeutically effective amount of an SLC to the mammal in combination with a checkpoint inhibitor, including monoclonal antibodies and small molecule inhibitors. Exemplary checkpoint molecules include CTLA-4, a CTLA-4 receptor, PD-1, PD1-L1, PD1-L2, 4-1BB, OX40, LAG-3, TIM-3 or a combination thereof. SLCs useful in the methods of the invention include SLC polypeptides, variants and fragments and related nucleic acids.