Embodiments of the disclosure include methods and compositions for enhancing expansion of immune cells for immunotherapy. In particular embodiments, immune cells, such as T-cells, express a constitutively active cytokine receptor in which the transmembrane and endodomains are able to provide an activating signal separately from any input to the corresponding exodomain to which they are operably linked. In specific embodiments, the transmembrane and endodomain from IL-7R is utilized with the exodomain of CD34.

Herein are provided anti-BCMA single domain antibodies (sdAb) prepared byte immunizing a llama with the ecto-domain of human B-cell maturation antigen (BCMA) that is preferentially expressed by mature B lymphocytes. By constructing a library of the heavy chain repertoire generated, VHH antibodies specific to the immunogen were isolated. The 13 unique example antibodies initially produced comprise CDR1, CDR2, and CDR3 sequences corresponding, respectively to SEQ NOs: 1-3, 4-6, 7-9, 10-12, 13-15, 16-18, 19-21, 22-24, 25-27, 28-30, 31-33, 34-36, 37-39; and related sequences. Also provided are multivalent antibodies comprising any one of the sdAbs, including bispecific T-cell engagers, bispecific killer cell engagers (BiKEs), and trispecific killer cell engagers (TriKEs). Also described are chimeric antigen receptors (CARs) for CAR-T therapy comprising any one of the aforementioned sdAbs. Uses of these molecules in the treatment of cancer or autoimmune diseases are also described, in particular hematological malignancies, such as multiple myeloma.

The present disclosure relates to mesothelin chimeric antigen receptors (CARs), T cell engaging molecules (TEAMs), anti-mesothelin-CAR T cells optionally comprising TEAMs, and methods of use thereof.

Provided herein are methods of treating a subject who has multiple myeloma and has received one to three prior treatment(s). Infusions of chimeric antigen receptor (CAR)-T cells comprising a CAR capable of specifically binding to an epitope of BCMA are administered to the subject.

Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. In various embodiments, the derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the use thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

Provided are methods of generating chimeric antigen receptors (CAR). In some embodiments, library screening of CAR is performed by generating a vector encoding the CAR from random attachment of vectors from libraries of vectors encoding antigen-binding domains (e.g., scFv regions), hinge regions, and endodomains. In some embodiments, the vectors contain a transposon.

Provided in the present invention are the preparation for a chimeric antigen receptor immune cell constructed on the basis of a growth arrest-specific protein 6 and the use of the chimeric antigen receptor immune cell. Specifically, provided in the present invention is a chimeric antigen receptor (CAR) based on GAS6 transformation. The CAR contains an extracellular binding domain, which can specifically target a GAS6 receptor. The CAR immune cell of the present invention has a strong specificity and target affinity, thereby also having a strong target cell killing capability and a high safety.

The invention provides methods of making immune effector cells (for example, T cells, NK cells) that express a chimeric antigen receptor (CAR), and compositions generated by such methods.

Disclosed are methods of making engineered cells comprising reduced Sirt6 expression as well as the cells that are the products of said methods. Thus, in one aspect, disclosed herein are engineered lymphocytes comprising reduced Sirt6 expression. Also disclosed herein are methods of treating cancer in a subject that involves collecting lymphocytes, such as tumor infiltrating lymphocytes (TILs), from the subject, treating the lymphocytes ex vivo to inhibit Sirt6 expression, and transferring the modified lymphocytes to a subject with a cancer.

The present invention provides a method of treating a patient diagnosed with Myxoid/Round cell liposarcoma with an anti-GPC3 therapeutic agent. The present invention also relates to quantification of GPC3 expression in tissue samples of patients diagnosed with Myxoid/Round cell liposarcoma by an immunostaining assay and identification of GPC3 expression levels that correlate with selection of patients for administering the anti-GPC3 therapeutic agent.