A preparation and an application of a chimeric antigen receptor immune cell constructed on the basis of granzyme B are provided, including, a granzyme B (GrB)-based modified chimeric antigen receptor (CAR), the CAR containing an extracellular binding domain, and the extracellular binding domain being capable of specifically targeting heat shock proteins. The CAR immune cell acts by means of binding of a ligand and a receptor, and has relatively high targeting specificity and relatively better safety.

As disclosed herein, high expression of the inhibitory ligands Galectin-3 (LAG-3 ligand), Galectin-9 (Tim-3 ligand), HMGB1 (Tim-3 ligand), CD112 (CD112R ligand) and TNFSF10 (DR5 ligand) in the microenvironment of triple negative breast cancer cells is inhibitory for T-cells. Therefore, disclosed herein is a chimeric receptor comprising an extracellular domain of TIM-3, LAG-3, CD112R or DR5 and transmembrane and intracellular domain of a pro-inflammatory interleukin and/or a co-stimulatory domain. Also disclosed is an immune effector cell engineered to express a chimeric antigen receptor (CAR) polypeptide and the disclosed chimeric receptor. Also disclosed is a method of providing an anti-cancer immunity in a subject with a MUC1-expressing cancer, the method comprising administering to the subject an effective amount of the disclosed immune effector cell, thereby providing an anti-tumor immunity in the subject.

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.

Disclosed herein are methods and compositions for cell-based immunotherapies that simultaneously target the tumor microenvironment (TME) via NKG2D ligands and tumor cells via tumor-associated antigens, specifically using immune effector cells as the platform due to their reduced toxicity against normal tissue. In some embodiments, immune effector cells co-express an NKG2D cytotoxic CAR and a CAR directed against a tumor-associated antigen that provides costimulatory signals to the immune effector cell, thus killing only in the presence of both antigens specifically within the TME. In contrast, within normal tissue that might express the tumor-associated antigen, but where self-HLA is also expressed, the costimulatory signal by itself is insufficient for immune effector cell activation, thereby preventing off-tumor toxicity.

Provided are antibodies that specifically bind to Vaccinia Virus B5 antigen (VV B5). In certain embodiments, the anti-VV B5 antibodies are humanized antibodies. Fusion proteins and conjugates comprising such antibodies are also provided. Pharmaceutical compositions comprising the antibodies, fusion proteins and conjugates of the present disclosure are also provided, as are methods of using such compositions, e.g., for therapy, in vivo imaging and/or the like. In certain aspects, provided are methods that comprise administering an antibody, fusion protein or conjugate of the present disclosure to an individual, wherein the individual comprises cells infected with VV, and wherein the antibody, fusion protein or conjugate is targeted to the infected cells by VV B5 antigens expressed on the surface of the infected cells.

Provided herein are multi-functional chimeric antigen receptor (CAR)-based compositions and their use in directing immune responses to target cells. The compositions have uses that include treating hyperproliferative disorders such as cancer. The provided methods generally include the use of a CAR cell in combination with an Adapter. The Adapter confers the ability to modulate, alter, and/or redirect CAR cell-mediated immune response in vitro and in vivo. In some embodiments, the CAR cell comprises a genetic modification to reduce or eliminate the expression of a targeted antigenic determinant.

The present invention provides compositions and methods comprising chimeric antigen receptors (CARs) wherein the Signal 1 has been optimized, for example wherein the CAR comprises an intracellular domain comprising a truncated version of CD3?, a FcR? or portion thereof, or a hybrid of CD3? and CD3?. Compositions and methods of treatment are also provided.

A modified immune cell and a use thereof in immunotherapy, the immune cell being a PD-1.sup.+T cell from peripheral blood. The immunotherapy is used in cancer treatment or treatment and prevention of diseases related to viral infections.

Some embodiments of the methods and compositions provided herein include methods and/or systems for increasing an activity of a cell comprising a chimeric antigen receptor (CAR), comprising use of a first nucleic acid encoding a transcription response element (TRE); and a second nucleic acid encoding a CAR, wherein the activity of the cell is increased compared to a cell lacking the first nucleic acid. In some embodiments, the increased activity of the cell is selected from: (i) survival of a subject administered the cell, wherein the subject comprises a target cell comprising an antigen, wherein the CAR is capable of specifically binding to the antigen; (ii) killing of a target cell comprising an antigen, wherein the CAR is capable of specifically binding to the antigen; and (iii) proliferation of the cell in the presence of a target cell comprising an antigen, wherein the CAR is capable of specifically binding to the antigen.

The present invention relates to the field of bioengineering, and in particular to a chimeric antigen receptor (CAR) expression vector and use thereof. The CAR expression vector comprising a polynucleotide encoding a CAR and full length or fragment of a polynucleotide encoding a granulocyte-macrophage colony-stimulating factor (GM-CSF). The CAR-GM-T cell constructed by the present invention is capable of expressing high-level GM-CSF, not only directly enhancing killing activity of the CAR-GM-T cell per se but also facilitating the infiltration of the CAR-GM-T cell into a solid tumor. The CAR-GM-T cell has a stronger immune modulation function compared to the conventional CAR-T cell and systematically triggers the endogenous anti-tumor immune response, thereby achieving superior therapeutic efficacy against a solid tumor.