Provided are methods of inducing differentiation and/or proliferation of T cells and uses thereof. In the present method, peripheral blood mononuclear cells (PBMCs) isolated from a subject are cultivated with bi-specific antibodies (BsAbs) in a culture medium so as to differentiate the PBMCs into the T cells. Each of the T cells has an anti-tumor antigen moiety and an anti-CD3 moiety on its surface. Also provided are methods and pharmaceutical kits for treating subjects suffering from cancers.

The present invention relates to genetically modified B cells and their uses thereof, for example, for the treatment of a variety of diseases and disorders, including cancer, heart disease, inflammatory disease, muscle wasting disease, neurological disease, and the like. In certain embodiments, the invention relates to an isolated modified B cell (CAR-B cell), capable of expressing a chimeric receptor (CAR-B receptor), wherein said chimeric receptor comprises (a) an extracellular domain; (b) a transmembrane domain; and (c) a cytoplasmic domain that comprises at least one signaling domain. In various embodiments, the invention comprises an isolated modified B cell, wherein said B cell is capable of expressing and secreting a payload, wherein the payload is not naturally expressed in a B cell or is expressed at higher levels than is naturally expressed in a B cell. In various embodiments, the payload is an antibody or fragment thereof.

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 invention relates to cell death inducing chimeric antigen receptors (D-CAR). In particular, the present invention relates to cell death inducing chimeric antigen receptors which comprise at least one death domain in their endodomain, including cell death inducing chimeric antigen receptors comprising within their death domains modifications which attenuate the self-association and/or binding to pro-apoptotic or pro-necrotic adaptor proteins, such as FADD or TRADD. Moreover, the present invention relates to an engineered immune cell expressing at its surface a cell death inducing CAR of the present invention and, optionally, an activating chimeric antigen receptor, wherein the extracellular ligand-binding domains of the cell death inducing CAR and the activating CAR bind to different antigens. The engineered immune cell may furthermore comprise at least one edited (e.g., inactivated) gene selected from TCR genes, immune check point genes, genes involved in drug resistance, and combinations thereof.

Anti-PSMA antibodies (e.g., UniAbs?) and CAR-T structures are disclosed, along with methods of making such antibodies and CAR-T structures, compositions, including pharmaceutical compositions, comprising such antibodies and CAR-T structures, and their use to treat disorders that are characterized by the expression of PSMA.

The present disclosure provides compositions and methods that rapidly and selectively modify cells of the immune system to achieve therapeutic objectives. The methods can be practiced in vivo and any cell type that expresses a known marker can be targeted for a therapeutic objective.

Disclosed are off-the-shelf immune effector cells that are engineered to express anti-CD3 antibodies disclosed herein that are configured to autoactivate the immune effector cells, thereby decreasing expression of T cell receptors (e.g. TCR??) that could result in GVHD. Also disclosed are methods for modifying donor immune effector cells to make them suitable for off-the-shelf treatment of allogeneic subjects. These methods involve engineering the cells to express an anti-CD3 antibody configured to activate the cells. In some embodiments, the antibody is a bi-specific antibody that binds the CD3 complex on the immune effector cells. In other embodiments, the antibody is a membrane bound anti-CD3 antibody that autoactivates the immune effector cell.

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 disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

The invention relates to chimeric antigen receptors (CAR) that comprise one or more single human variable domain antibody and cells that express such CAR. In particular, the invention relates to CARs that include multiple single human variable domain antibodies. In a particular embodiment, the one or more single human variable domain antibody binds to prostate membrane antigen.