Provided are a preparation method for a CTL cell and an application thereof. The preparation method comprises the following steps of: inducing a CTL cell by using a tumor antigen PAP-GM-CSF sensitized DC cell; and knocking out a PD-1 gene of the CTL cell to obtain a PD-1 knock-out CTL cell. The CTL cell obtained by the preparation method can be used for preparing drugs for treatment of prostate cancer, especially for treating PAP-positive prostate cancer. The CTL cell does not cause CTL cell failure and anergy due to the tumor-expressed PD-L1 after being transfused into the body, thereby producing efficient specific cytotoxic effect on a tumor cell and improving the curative effect and reducing the side effect.

Embodiments provided for herein relate to compositions and methods related to chimeric proteins that can be used to modulate a subject's immune system and, for example, treat cancer.

Provided herein are compositions and methods for improving immune system function. In particular, provided herein are compositions, methods, and uses of YY1 and EZH2 inhibitors for preventing and reversing T-cell exhaustion (e.g., for use in immunotherapy).

Described herein are compositions and methods for treating a disease, particularly a cancer, with an immune checkpoint modulatory agent and a strain of an Arbovirus or a strain of an Alphavirus. Also provided herein are also methods for combination therapy comprising administration of an immune checkpoint modulatory agent, tumor antigen primed dendritic cells and an Alphavirus or an Arbovirus.

The invention provides compositions and methods for treating diseases associated with expression of CD19, e.g., by administering a recombinant T cell comprising the CD19 CAR as described herein, in combination with one or more B-cell inhibitors, e.g., inhibitors of one or more of CD10, CD20, CD22, CD34, CD123, FLT-3, ROR1, CD79b, CD179b, or CD79a. The disclosure additionally features novel antigen binding domains and CAR molecules directed to CD20 and CD22, and uses, e.g., as monotherapies or in combination therapies. The invention also provides kits and compositions described herein.

The present disclosure provides modified immune cells (e.g., modified T cells) comprising a chimeric antigen receptor (CAR) having affinity for a prostate-specific membrane antigen (PSMA) (e.g., human PSMA). The present disclosure provides modified immune cells (e.g., modified T cells) comprising a CAR having affinity for PSMA and a dominant negative receptor and/or a switch receptor. The present disclosure provides modified immune cells (e.g., modified T cells) comprising a CAR having affinity for PSMA and a dominant negative receptor and/or a switch receptor, wherein the modified cell is capable of expressing and secreting a bispecific antibody.

The present invention as described herein is aimed at combining a radiation-induced immunogenic effect with a T-cell therapy technique to markedly improve the therapeutic effectiveness of adoptive T-cell therapy with minimized toxicity. The method of this invention comprises, identifying a target tumor, applying ablative radiation treatment to the tumor in-situ, waiting for the production of CTLs primed by antigen presenting cells (APC), then resecting the target tumor from the patient. The CTLs are harvested and isolated from the tumor and undergo ex-vivo expansion and subsequent treatment of immune checkpoint blockades. The expanded CTLs are then infused back into the patient for systemic treatment of microscopic disease. The primed CTLs that are induced by radiation in-situ, are used as the source of T-cell therapy or other types of cell therapy. The harvested CTLs will have high tumor specificity with a wide range of heterogeneous tumor associated antigens (TAA) presentation.

Provided herein are compositions, methods, and uses involving bispecific binding molecules that specifically bind to HER2, a receptor tyrosine kinase, and to CD3, a T cell receptor, and mediate T cell cytotoxicity for managing and treating disorders, such as cancer. Also provided herein are uses and methods for managing and treating HER2-related cancers.

Control Devices are disclosed including RNA destabilizing elements (RDE), and RNA control devices, combined with transgenes, including Chimeric Antigen Receptors (CARs) in eukaryotic cells. RDEs can be combined with RNA control devices to make RDEs that include ligand mediated control. These smart RDEs and other RDEs can be used to optimize expression of transgenes, e.g., CARs, in the eukaryotic cells so that, for example, effector function is optimized. CARs and transgene payloads can also be engineered into eukaryotic cells so that the transgene payload is expressed and delivered at desired times from the eukaryotic cell.

The invention provides improved compositions for adoptive immune effector cell therapies for treatment, prevention, or amelioration of numerous conditions including, but not limited to cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency.