Described herein are immune cells comprising: a T-cell receptor (TCR) and a chimeric stimulating receptor (CSR) that comprises (i) a ligand-binding module that is capable of binding or interacting with a target ligand; (ii) a transmembrane domain; and (iii) a CD30 costimulatory domain, in which the CSR in the immune cells lacks a functional primary signaling domain. Also provided herein are methods of using the same or components thereof (e.g., the CSR) for therapeutic treatment of cancers (e.g., solid tumor cancers).

Provided herein are populations of placental-derived natural killer cells comprising a cleavage resistant CD16. Also provided are methods of treating diseases, disorders or conditions in a human subject comprising administering to the subject an effective amount of a population of placental-derived natural killer cells comprising a cleavage resistant CD16 to the subject so as thereby to provide an effective treatment of the to the subject. The cells, such as CYNK cells, can be placental CD34+ cell-derived natural killer (NK) cells. The diseases, disorders or conditions include cancers such as multiple myeloma and lymphoma. The present invention also provides compositions comprising populations of placental-derived natural killer cells comprising a cleavage resistant CD16 for the treatment of a subject and methods of their use.

Provided are a humanized antibody specifically binding to EpCAM, and a chimeric antigen receptor, a nucleic acid, a vector, a cell, and the use associated with the humanized antibody. The humanized antibody comprises a heavy chain variable region and a light chain variable region. The sequence of the heavy chain variable region comprises a sequence shown in SEQ ID.1, a sequence shown in SEQ ID.2 and a sequence shown in SEQ ID.3. The sequence of the light chain variable region comprises a sequence shown in SEQ ID.4, a sequence shown in SEQ ID.5, and a sequence shown in SEQ ID.6. After the humanized antibody is constructed as a chimeric antigen receptor-T Cell, EpCAM-positive tumor cells can be specifically identified and killed, and tumors can be cleared in an animal body.

Provided herein are compositions and methods for reducing neuroinflammation and treating neurodegenerative diseases using proteinase inhibitors. The invention also provides methods for reducing post-injury scar formation in the central nervous system.

The present invention provides a method for treating a disease in a subject, which comprises the step of administering to the subject a plurality of cells which express: (a) a chimeric antigen receptor (CAR); and (b) a mutant version of calcineurin A and/or calcineurin B which is resistant to the calcineurin inhibitor. The subject may be receiving or have received treatment with a calcineurin inhibitor. The CAR-expressing cells may be administered prior to, following, simultaneously with or in combination with a calcineurin inhibitor.

The present disclosure describes systems and methods for immunotherapies Immune cells can be engineered to exhibit enhanced half-life as compared to control cell (e.g., a non-engineered immune cell). Immune cells can be engineered to exhibit enhanced proliferation as compared to a control cell. Immune cells can be engineered to effectively and specifically target diseased cells (e.g., cancer cells) that a control cell otherwise is insufficient or unable to target. The engineered Immune cells disclosed herein can be engineered ex vivo, in vitro, and in some cases, in vivo. The engineered Immune cells that are prepared ex vivo or in vitro can be administered to a subject in need thereof to treat a disease (e.g., myeloma or solid tumors). The engineered Immune cells can be autologous to the subject. Alternatively, the engineered immune cells can be allogeneic to the subject.

The generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

The present invention relates to, inter alia, compositions and methods, including engineered T cells that express chimeric antigen receptors and heterologous chimeric proteins that find use in the treatment of cancer.

Described herein are single vectors that, when expressed in cytolytic immune cells, results in both the expression of (1) a CAR targeting tumor-associated antigens and (2) secretion of a bispecific antibody that on one end recognizes NKG2D expressed on both innate and antigen specific cytolytic immune cells and on the other end targets tumor associated antigens. Unexpectedly, these modifications to the T cells result in enhanced survival and proliferation in vivo. Thus, therapeutic and diagnostic uses are disclosed.

Provided herein are methods of treating cancer in a subject including detecting an amount of PD-L1(+) natural killer (NK) cells in a biological sample from the subject and treating the subject with an anti cancer therapy. Provided herein are methods of treating cancer in a patient including isolating natural killer (NK) cells from a subject, producing a population of PD-L1(+) NK cell from the isolated NK cells, and administering the population of PD-L1(+) NK cells into the patient.