The present disclosure relates to promoter constructs comprising: one or more heat shock elements: a core promoter; and a gene of interest: vectors comprising the promoter constructs, and immune cells modified to include the promoter constructs. The promoter constructs provide the ability to remotely control immune cell therapies by thermal targeting. The present disclosure also provides methods of use for the promoter constructs.

Embodiments of the present disclosure include methods and compositions related to CD70-targeting polypeptides. In certain aspects, anti-CD70 antibodies are disclosed. In some aspects, disclosed are chimeric receptors engineered to bind to CD70. Also disclosed are immune cell engagers comprising a CD70-binding region and one or more immune cell binding regions. Cells (e.g., NNK cells, T cells) expressing CD70-targeting peptides are described. Also described are therapeutic methods using polypeptides of the disclosure.

Disclosed herein are polynucleotides encoding ligand-inducible gene switch polypeptides, and systems comprising gene switch polypeptides for modulating the expression of a heterologous gene and an interleukin in a host cell. The compositions, methods and systems described herein facilitate ligand dependent expression of polypeptides including but not limited to cytokines and antigen binding polypeptides.

Disclosed herein are polynucleotides encoding ligand-inducible gene switch polypeptides, and systems comprising gene switch polypeptides for modulating the expression of a heterologous gene and an interleukin in a host cell. The compositions, methods and systems described herein facilitate ligand dependent expression of polypeptides including but not limited to cytokines and antigen binding polypeptides.

Disclosed herein is an optimized CD99-targeting chimeric antigen receptor and application thereof, wherein a signal peptide, a single-chain antibody ScFv, strepII, a CD8 hinge, a CD28 transmembrane region, a CD28 intracellular domain, an intracellular co-stimulatory domain 4-1BB and CD3? chain are sequentially spliced in the chimeric antigen receptor is from the N-terminal to the C-terminal. The single-chain antibody ScFv can specifically recognize CD99 protein on the surface of tumor cells. The CD99-targeting chimeric antigen receptor is used to modify immune cells for the treatment of surface CD99-positive tumors.

The present invention is directed to the field of immunotherapy. Specifically, the invention provides improved cell compositions and methods for adoptive cell therapy, useful in the treatment of cancer. More specifically, embodiments of the invention employ the use of cell compositions comprising a high proportion of activated cytotoxic CD8.sup.+ cells and in particular CD8.sup.+NKG2D.sup.+granzyme-B.sup.+ cells characterized by enhanced cytotoxicity, to processes for their preparation from peripheral blood mononuclear cells (PBMC), and to their use in cancer management.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to Mexpress chimeric antigen receptors as well as genetically edited or otherwise engineered to alter the effectiveness with which another immune cell can target and induce cytotoxic effects on the engineered cells. In several embodiments, the methods and compositions disclosed herein reduce fratricide within a therapeutic cell population, which in some instances comprises mixture of immune cell types. Additionally, the methods and compositions disclosed herein enhance one or more aspects of the efficacy of the immune cells in cellular immunotherapy including cytotoxicity and/or persistence, as well as reduced graft versus host or host versus graft effects.

Disclosed herein are methods and compositions for modulating immune responses by using decoy molecules to bind to soluble or other ligands. In specific embodiments, the decoy molecules comprise a domain that binds to a target immunosuppressive ligand and another domain that releases immunostimulatory signals when activated. In specific embodiments, the decoy molecules are soluble and are secreted by transgenic T cells at a tumor site, such as upon antigen engagement, and they protect the transgenic cells themselves and also bystander (e.g., non-modified) endogenous immune cells.

Disclosed herein are isolated nucleic acid molecules comprising a polynucleotide encoding a chimeric antigen receptor (CAR) comprising an antibody that specifically recognizes human mesothelin, a CD8 hinge region, a CD8 transmembrane region, a 4-1BB intracellular region and a CD3 intracellular region; a polynucleotide encoding IL-7; and a polynucleotide encoding CCL19. Also disclosed herein include vectors, modified immune cells, and pharmaceutical compositions comprising the nucleic acid molecules and methods of use.

The present invention relates, in part, to chimeric proteins, chimeric protein complexes, vaccine compositions, and adjuvants that include IL-1 or pro-IL-1 and their use as therapeutic agents or vaccines. The present invention further relates to methods of treatment of various diseases, such as infectious diseases and cancer and methods of vaccination.