The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

Described herein is a reliable method for preparing a potent vaccine useful for immunotherapy comprising the step of cryopreserving a population of cells undergoing immunogenic cell death, and using such cells to activate dendritic cells for use in immunotherapy. In a specific embodiment, the method comprises cryopreserving cancer cells undergoing cell death, which can be used to prepare a pharmaceutical composition for immunotherapy against cancer.

The present invention provides chimeric antigen receptor (CAR)-T cells modified to express a CAR fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) comprising V.sub.H and V.sub.L, wherein scFv has an activity against a tumor antigen CD19, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain; wherein the fusion protein further comprises a FLAG tag N-terminus to scFv, C-terminus to scFv , or between V.sub.H and V.sub.L. Using CD19-FLAG CAR-T cells instead of CD19 CAR-T cells, cytokine levels (Interferon-?, IL-2 and IL6) caused by infused CAR-T cells are reduced.

The present invention relates to augmenting the effects of adoptive T cell therapy, such as TVAX Immunotherapy, using adjunct treatment with an oncolytic virus, such as a vaccinia virus, to treat various types of cancer or other proliferative disorders. Immunomodulatory compounds can be used to further augment to effects of the therapy.

A method of carrying out adoptive immunotherapy by administering a subject an antigen-specific cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount is described. In the method, the CTL preparation is preferably administered as a preparation of an in vitro antigen-stimulated and expanded primate CTL population, the CTL population: (i) depleted of FoxP3+ T lymphocytes prior to antigen stimulation, (ii) antigen-stimulated in vitro in the presence of interleukin-21; or (iii) both depleted of FoxP3+ T lymphocytes prior to antigen stimulation and then antigen-stimulated in vitro in the presence of interleukin-21. Methods of preparing such compositions, and compositions useful for carrying out the adoptive immunotherapy, are also described.

The present invention belongs to the field of biomedicine, and particularly relates to a chimeric antigen receptor and use thereof. The present invention provides a novel chimeric antigen receptor, comprising an extracellular domain, a transmembrane domain and an intracellular domain, wherein the transmembrane domain and the intracellular domain of the chimeric antigen receptor form a costimulatory signaling domain, and the costimulatory signaling domain comprises a full length or a fragment of an amino acid sequence encoding a reverse dectin-1. Experiments prove that novel CAR-T cells provided by the present invention are effective against a variety of solid tumors and hematological malignancies.

The present disclosure relates to identifying novel tumor immune evasion targets. A CRISPR activation screen was employed to identify novel checkpoint inhibitor targets, where upon upregulation, conferred tumor resistance to cytotoxic T cells in model cancer cell lines. Using MAGeCK and FDR analyses to identify candidate genes that were enriched in cancer cells, B3GNT2, MCL1, BCL2A1 and JUNB were identified as the most enriched after a pathway analysis of the top 576 genes prioritized by MAGeCK. Currently, these four genes have not been identified or suggested as possible checkpoint inhibitor targets. Provided herein are methods of targeting the expression or activity of B3GNT2, MCL1, BCL2A1 and JUNB using small molecule agents and/or gene editing methods with the aim of enhancing anti-tumor immunity in subjects in need thereof.

The invention provides compositions and methods for treating diseases associated with expression of a tumor antigen as described herein. The invention also relates to the methods of preconditioning a subject, e.g., by depleting B cells in combination with the use of a cell comprising a chimeric antigen receptor (CAR) that targets a tumor antigen as described herein. The methods for preconditioning the subject described herein include using a cell comprising a CAR that targets a B cell antigen as described herein.

An industrial preparation of natural killer cells (NKs) is produced by: using umbilical cord blood and peripheral blood from legitimate sources as raw materials, obtaining stem cells by a method for extracting and separating karyocytes, or using FICOLL? or PERCOLL? density gradient media centrifugation to isolate and screen out karyocytes; diluting the above-mentioned karyocytes with cell culture medium, adding interferon, interleukin, CD3 antibody, and human albumin, loading them together into a bioreactor for perfusion culture, and then performing multiplication culture; the passage number of natural killer cells from multiplication culture is no less than 8, and the culture time is no less than 4 weeks; the markers of the natural killer cells obtained after the multiplication culture are CD3.sup.?\CD56.sup.+, CD16.sup.+, CD57.sup.+, and CD8.sup.+, wherein CD16.sup.+/CD56.sup.+?15%, CD3.sup.?/CD56.sup.+?50%, and CD8.sup.+/CD57.sup.+?8%; then preparing an injection with a certain concentration using the cell suspension obtained by above-mentioned method.

The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.