Production and use of novel therapeutic cells, called T-Vehicles, in the allogeneic Adoptive Cell Therapy setting allows a wide range of therapeutic benefits to accrue with minimal or no risk of GVHD. T-Vehicles are created from donor T cells that are altered to contain therapeutic attributes that do not include their native antigen receptors and can deliver therapeutic benefits irrelevant of their native antigen specificity. T-Vehicles can possess highly restricted native antigen specificity that renders them unable to recognize antigens present on normal cells and incapable of initiating GVHD, making them ideal transport vehicles to deliver various therapeutic attributes in vivo. In essence, production and use of T-Vehicles is a paradigm shift that opens the door to therapeutic application of T cells in ways not previously contemplated, independent of whether or not there is an HLA match between the donor and the recipient.

The present application provides single-domain antibodies targeting BCMA, and chimeric antigen receptors (such as monovalent CAR, and multivalent CAR including bi-epitope CAR) comprising one or more anti-BCMA single-domain antibodies. Further provided are engineered immune effector cells (such as T cells) comprising the chimeric antigen receptors. Pharmaceutical compositions, kits and methods of treating cancer are also provided.

The present invention relates to a cell which co-expresses: (i) a first chimeric antigen receptor (CAR) at the cell surface, comprising an antigen-binding domain which binds to CD19; (ii) a second CAR at the cell surface, comprising an antigen-binding domain which binds to CD22; (iii) dominant negative SHP2 (dSHP2); and (iv) dominant negative TGF receptor II (dnTGFRII).

Provided are modified cells and methods for their use in treating cancer. The cells are modified to express and secrete a Bi-specific T cell engager (BiTE) that includes a segment that specifically binds to human Folate Receptor alpha (FR) and a segment that that specifically binds to human CD3, such as CD3e. The modified cells can be T cells. Methods for producing the modified cells are also provided.

The invention relates to a nucleic acid encoding, an artificial T cell receptor, or a fragment of an artificial T cell receptor, wherein the nucleic acid is operatively linked to a transcriptional regulatory sequence, and wherein the transcriptional regulatory sequence comprises a binding domain for a transcription factor that promotes a regulatory T lymphocyte phenotype and cells comprising such nucleic acids. The cells may further comprise a nucleic acid encoding the transcription factor and a targeting polypeptide. The cells of the invention are useful in medicine, in particular in the treatment of inflammatory conditions.

The current application fulfills a need for methods of making bi-specific CAR T-cells that have high efficacy. Aspects of the disclosure relate to a method for manufacturing a CD19/CD20 bi-specific chimeric antigen receptor (CAR) T cell comprising the ordered steps of: (a) providing a composition comprising a population of cells comprising T cells; (b) contacting the composition comprising the population of cells comprising T cells with one or more of a transactivating composition, IL-2, and/or IL-15; (c) transducing the cell composition from (b) with a CD19/CD20 bi-specific CAR nucleic acid; and (d) removing the transactivating composition from the cell composition of (c). Further aspects relate to a population of CD19/CD20 bi-specific CAR-T cells produced by the methods of the disclosure. Yet further aspects describe a method for treating a subject for B-cell lymphoma comprising administering cells of the disclosure.

Embodiments of the disclosure provide compositions, kits, and methods for allogeneic hematopoietic cell transplantation (alloHCT) to patients. In an embodiment, a therapeutic composition for alloHCT includes at least first and second populations of isolated CD45+ cells (ICC). At least a portion of the CD45+ cells in the first population may have an antibody bound to a marker on the cell surface which is used to separate CD34+ cells from a mixture of nucleated cells (MNC) from donor or invitro produced blood. The MNC may comprise various cell types in various amounts, for example, about 70% CD34+ cells, less than about 5% CD3+ cells and less about 20% granulocytes. The ICC's in the second population include regulatory T cells which are typically at least about 50% of the population. Embodiments of the disclosure are particularly useful for treatment of hematologic cancers (e.g., leukemia, lymphoma), sickle cell anemia, GVHD, autoimmune and other diseases.

CAR Tregs and Tregs are provided which are both conversion-resistant and condition-resistant. The Treg cells are engineered such that they are deficient in or substantially devoid of a cell-surface marker or antigen.

Provided herein are compositions and methods for the treatment of cancers using modified TILs, wherein the modified TILs include one or more immunomodulatory agents (e.g., cytokines) associated with their cell surface. The immunomodulatory agents associated with the TILs provide a localized immunostimulatory effect that can advantageously enhance TIL survival, proliferation and/or anti-tumor activity in a patient recipient. As such, the compositions and methods disclosed herein provide effective cancer therapies.

Provided are a chimeric antigen receptor immune cell, and a preparation method therefor and an application thereof. The surface of the chimeric antigen receptor immune cell expresses a receptor targeting a specific antigen, and also expresses a signal conversion protein. The signal conversion protein is a fusion protein containing a dominant negative receptor TGFBR2 extracellular element and an IL-7R intracellular element. The chimeric antigen receptor immune cell can further convert, by means of the signal conversion protein, the inhibitory signal of a TGF- immunosuppressive factor in a tumor microenvironment that is not conducive to the survival of immune cells into a cytokine activation signal, thereby significantly enhancing the survival of the immune cells and having a more sustained tumor killing effect.