Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. 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 used thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

Provided herein are methods for treating a patient with HIV, cancer, a viral infection, or a bacterial infection, comprising administering an effective amount of activated lymphocytic cellular compositions. Related compositions, kits, and methods for modulating the immune system using the activated lymphocytic cellular compositions are also provided.

Provided are a cancer-antigen-specific Natural Killer (NK) cell including a non-viral expression plasmid encoding a chimeric antigen receptor, wherein the chimeric antigen receptor comprises a cancer-antigen-specific single-chain variable fragment (scFv), a hinge region, a transmembrane domain, and intracellular domains; methods of generating said cancer-antigen-specific NK cell; a bispecific antigen-binding molecule comprising a first antigen-binding molecular and a second antigen-binding molecular, wherein the first antigen-binding molecular is an scFv specific to a cancer antigen, and the second antigen-binding molecule is specific to a second cancer antigen and an NK cell receptor, and comprises at least one of an scFv and and an aptamer-based molecule; pharmaceutical compositions comprising at least one of the cancer-antigen-specific NK cell and the bispecific antigen-binding molecule; and methods of treating cancer patients using the pharmaceutical compositions.

Disclosed herein is a method for enhancing adoptively transferred autologous or allogeneic immune effector cells (T cells) in patients who are HLA-C1+. In some embodiments, the method involves ablating KIR2DL2 expression in the T cells prior to adoptive transfer. In some embodiments, the T cells are further engineered to express a CAR. Therefore, disclosed herein are enhanced CAR-T cells that are engineered to have ablated KIR2DL2 expression or activity.

The disclosure relates to immune cells comprising systems of two engineered receptors each having a ligand binding domain, collectively designed to target cells identified by loss of heterozygosity and used to treat a disease or disorder, for example, cancer. The disclosure provides immune cells expressing two engineered receptors, methods of making same, and polynucleotides and vectors encoding same.

The invention relates to nucleic acid constructs comprising a combination of a first sequence encoding a CAR and second sequence encoding an amino acid transporter, and to cells comprising such nucleic acid constructs. It also relates to methods of manufacturing said cells, and to pharmaceutical compositions comprising said nucleic acid constructs or cells, for use in the treatment of diseases with cellular amino-acid depletion such as cancer.

Compositions and methods for treating diseases associated with expression of cluster differentiation 33 (CD33) and/or cluster differentiation 5 (CD5) involve two chimeric antigen receptors (CARs) specific to CD33 and CD5 and T cells with CD33 and CD5 dual-CAR. Methods of administering a genetically modified T cell expressing the dual-CAR can be used for autologous and allogeneic treatment of T cell malignancies.

The present disclosure provides BCMA-targeted chimeric antigen receptors (CARs) as well as preparation methods and applications thereof. The CARs of the present disclosure targets BCMA-positive cells, and can be used for treating BCMA-positive B-cell lymphoma, multiple myeloma and plasma cell leukemia.

A method of manipulating allogeneic cells for use in allogeneic cell therapy providing a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism, or Mirror Effect. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the mirror of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The mirror of the GVH effect is the host vs. graft (HVG) effect The anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in a patient.

In various embodiments, the present disclosure provides chimeric antigen receptors (CARs) which bind to mesothelin. The mesothelin CARs comprise an extracellular region comprising a binding domain that specifically binds to at least a portion of mesothelin, a transmembrane region, and an intracellular region comprising an effector domain or a portion or variant thereof and a costimulatory domain or a portion or variant thereof. Recombinant host cells expressing the mesothelin CARs are also provided, as well as compositions and methods of treatment, prevention, and manufacture comprising the same.