Compositions and methods for cellular genome engineering that permit simple and efficient targeted knock-in of a CAR and simultaneous knockout of individual genes are described. The compositions and methods are especially applicable to massively parallel engineering, selection, and identification of CAR T cell variants exhibiting a desired phenotype. AAV vectors containing crRNA and CAR expression cassettes and homology arms for targeted genomic integration thereof are provided. Also provided are libraries containing a plurality of AAV vectors and methods of use thereof in screens for identifying desirable CAR T cell variants. Methods of treatment using CAR T cell variants exhibiting improvements in one or more phenotypes are also provided.

Provided are a simple and convenient method for preparing universal immune cells and the use thereof. The method comprises placing allogeneic immune cells and specific cell mitogens, cytokines, and immunologic adjuvants in a liquid cell culture medium to be co-cultured in a culture container, so as to obtain a universal immune cell culture with a high immunocompetence. Many clinical long-term practical applications have proven that the universal immune cells are safe and reliable, durable and effective, and have no rejection reaction. Therefore, the universal immune cells can be used as maternal cells of other types of universal immune cell preparations, such as CAR-T and TCR-T, and can be used in fields including adoptive cellular immunotherapy, etc.

The present invention relates to an in vitro cell culture method comprising a step of contacting T-cells with an MPC inhibitor, and further to a cell population comprising T-cells with a memory phenotype obtained by said method, preferably, wherein the T-cells are human cells. The present invention also relates to a method for generating and/or maintaining T-cells and/or B-cells with a memory phenotype comprising the steps of culturing T-cells and or B-cells in vitro and adding an MPC inhibitor to the culture. The invention furthermore relates to a population of T-cells and/or B-cells obtained by the methods of the invention. Also provided are immunotherapies using the cells of the invention. Furthermore, provided is an MPC inhibitor for use in immunotherapy and/or as a vaccine co-adjuvant.

Described herein is a therapeutic cell that expresses a fusion protein comprising: (a) a target-binding domain; and (b) a degradation domain, e.g., a degron or E3 ligase-recruiting domain, that is heterologous to the target-binding domain. In the therapeutic cell, binding of the fusion protein to a target protein via the target-binding domain induces degradation of the target protein. The therapeutic cell can be an immunostimulatory cell, an immunoinhibitory cell or a stem cell, for example. Methods of treatment using the cell are also provided.

The present disclosure provides a population of poly-donor CD4.sup.IL-10 cells generated by genetically modifying CD4.sup.+ T cells from at least three different T cell donors. Further provided are methods of generating the poly-donor CD4.sup.IL-10 cells and methods of using the poly-donor CD4.sup.IL-10 cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, and other immune disorders.

The present disclosure provides modified immune cells or precursors thereof (e.g. T cells) comprising a chimeric antigen receptor (CAR) capable of binding human PSCA. CARs capable of binding human PSCA, and nucleic acids encoding the same are also provided. Provided herein are bispecific CARs capable of binding human PSCA and human PSMA, nucleic acids encoding the same, and modified immune cells comprising the same. Modified immune cells comprising a PSMA CAR and a PSCA CAR are also provided. Compositions and methods of treatment are also provided.

The disclosure relates to methods of diagnosis and prognosis, compositions for immunotherapies, methods of improving said compositions, and immunotherapies using the same (e.g., T cells, non-T cells, TCR-based therapies, CAR-based therapies, bispecific T-cell engagers (BiTEs), and/or immune checkpoint blockade).

The present invention relates generally to immunotherapy, in particular immunotherapy for treating cancer, infectious diseases or autoimmune diseases. More specifically, the invention relates to Mucosal-Associated Invariant T (MAIT) cells expressing Chimeric Antigen Receptors (CARs), wherein the MAIT cell is allogenic with respect to the subject to be treated.

Some embodiments of the methods and compositions provided herein relate to modulating signaling of anti-hapten CAR T cells, such as anti-fluorescein CAR T cells, by the use or administration of an unconjugated hapten, such as unconjugated fluorescein or a salt or derivative thereof.

Provided are therapeutic agent including nucleic acid and CAR-modified immune cell and the use thereof. The therapeutic agent comprises first composition and second composition, the first composition comprises a nucleic acid having a labeling polypeptide coding sequence for being introduced into a tumor cell and/or a cancer cell; the labeling polypeptide has an extracellular antigen determining region, a spacer portion, and a transmembrane portion that are operatively linked, which can be expressed to form modification on the surface of the tumor cell and/or cancer cell; the extracellular antigen determining region comprises one or more epitope polypeptides; wherein, amino acid sequences of proteins on cell membrane or secreted proteins of mammal do not comprise the epitope polypeptide amino acid sequence in the natural state; the second composition comprises chimeric antigen receptor modified immune cell which specifically recognize and bind to the extracellular antigen determining region. The therapeutic agent achieves synergistic therapeutic effect.