The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

The invention relates to compositions comprising a CD4 lymphocyte depleting agent; and methods of using the compositions to treat, prevent, reduce the severity of and/or slow the progression of a condition in a subject. The invention also relates to use of combinations of a CD4 lymphocyte depleting agent and at least one additional agent to treat, prevent, reduce the severity of and/or slow the progression of a condition in a subject. The additional agent may be an immune check point inhibitor, an adoptive immune therapeutic, an immune adjuvant, or an immune modulating agent, or their combinations.

Provided herein are methods for the production of tissue resident memory-like T cells by the combination of hypoxia and TGF. Further provided herein are methods of using the tissue resident memory T cells as adoptive cell therapy.

The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

Provided are methods of producing an isolated population of T cells, the method comprising culturing isolated T cells in vitro in the presence of hydroxycitric acid, and/or a salt thereof, wherein the salt is potassium hydroxycitrate or sodium hydroxycitrate. Also provided are related isolated populations of cells, pharmaceutical compositions, and methods of treating or preventing cancer in a mammal.

The present invention encompasses methods and compositions for the generation and use of cytotoxic T lymphocytes that target multiple viruses or that are specific for multiple tumor antigens. In specific embodiments, the generation methods employ use of certain cytokines to promote proliferation and reduce cell death in an activated T cell population and/or that employ a particular bioreactor having a gas permeable membrane.

Provided herein are methods for the production of tissue resident memory-like T cells by the combination of hypoxia and TGF. Further provided herein are methods of using the tissue resident memory T cells as adoptive cell therapy.

The present invention provides a novel complex for use in the prevention and/or treatment of glioma, in particular glioblastoma, 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 glioma, in particular glioblastoma, such as a pharmaceutical compositions and vaccines are provided.

The present application provides TILs comprising agents that enhance activity and/or proliferative capacity of the TILs, methods of manufacturing such TILs, and methods of using such modified TILs for enhancing an immune response.

Therapeutic modalities are provided for targeting adoptive cellular therapies to specific sites of disease, involving the use of specific repertoirs of PRR ligands. In effect, innate immune system signaling is provoked so as to facilitate the homing of adoptive immune cells to sites of disease, for example to the site of a solid tumor.