Aspects of the present disclosure are directed to methods for treating a subject having pancreatic cancer. Certain aspects relate to treatment with cancer immunotherapy, including immune checkpoint blockade therapy. In some cases, a subject has been determined to have or to have had an inflammatory condition, such as pancreatitis. Further aspects relate to methods for identifying a subject as a candidate for an immune checkpoint blockade therapy.

A tumor or a malignant disease can be treated by the combined administration of mesenchymal stem cells (MSCs) with an anti-tumor immunotherapy. The MSCs need not be genetically modified, and do not include exogenous nucleic acids that encode immune response-stimulating cytokines. The anti-tumor immunotherapy can be a cellular immunotherapy, such as administration of chimeric antigen receptor (CAR) T cells, in which the T cell receptor binds specifically to a tumor-associated antigen.

The present invention provides a chimeric antigen receptor (CAR) that recognizes B7-H3 (CD276), as well as methods of use in the treatment of diseases and disorders.

A preparation and an application of a chimeric antigen receptor immune cell constructed on the basis of a C-type lectin superfamily low-density lipoprotein receptor (LOX1) are provided. Specifically provided is a chimeric antigen receptor (CAR) modified on the basis of LOX1. The CAR contains an extracellular binding domain capable of specifically targeting LOX1 receptors such as heat shock protein, oxidized low-density lipoprotein (oxLDL) and phosphatidylserine. The CAR immune cell has strong specificity and target affinity, and therefore has strong target cell killing capability and a high degree of safety.

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.

Disclosed herein are chimeric antigen receptors (CARs) that target MUC1*. In some embodiments, the CARs have been optimized to reduce T cell exhaustion.

Disclosed herein are chimeric antigen receptors (CARs) that target MUC1*. In some embodiments, the CARs have been optimized to reduce T cell exhaustion.

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.

Provided herein are nucleic acids, expression cassettes, modified lymphocytes and compositions comprising the same which include a sequence encoding a gene of Table 1. In some embodiments, the gene is LTBR. In certain embodiments, the cell is a T cell. In certain embodiments, the cell further comprises a CAR or engineered TCR. Methods of treatment using the provided compositions are also described.

The present invention provides a universal, yet adaptable, anti-tag chimeric antigen receptor (AT-CAR) system which provides T cells with the ability and specificity to recognize and kill target cells, such as tumor cells, that have been marked by tagged antibodies. As an example, ?FITC-CAR-expressing T cells have been developed that specifically recognize various human cancer cells when those cells are bound by cancer-reactive FITC-labeled antibodies. The activation of ?FITC-CAR-expressing T cells is shown to induce efficient target lysis, T cell proliferation, and cytokine/chemokine production. The system can be used to treating subjects having cancer.