Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. The iPSC-derived effector 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.

The present invention relates to autologous dual-specific lymphocytes, methods of making and uses for the treatment of tumors. In particular, the invention relates to methods producing autologous dual-specific lymphocytes comprising an endogenous receptor for at least one tumor associated antigen and an exogenous receptor for a strong antigen

Embodiments described herein relate to compositions including genetically modified CAR cells and uses thereof for treating cancer. Some embodiments of the present disclosure relate to compositions and methods for T cell response enhancement and/or CAR cell preparation. For example, a method may include obtaining cells comprising a CAR and culturing the cells in the presence of an agent that is recognized by the extracellular domain of the CAR.

The present invention relates to autologous dual-specific lymphocytes, methods of making and uses for the treatment of tumors. In particular, the invention relates to methods producing autologous dual-specific lymphocytes comprising an endogenous receptor for at least one tumor associated antigen and an exogenous receptor for a strong antigen.

Provided herein are antibodies and chimeric priming receptors that bind PSMA and antibodies and chimeric antigen receptors that bind CA9. Also provided are systems of chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9, cells expressing such systems, and methods of use thereof.

This document relates to methods and materials related to isolated polypeptides, polypeptide preparations, and methods for using one or more isolated polypeptides to activate T cells. For example, polypeptides that can be used to activate T cells to generate antigen-specific T cells are provided. In some cases, T cells activated as described herein can be administered to a mammal having cancer (e.g., MM) or a precancerous condition (e.g., MGUS) to treat the mammal (e.g., to induce an immune response against the cancer or the precancerous condition).

Methods are disclosed for producing defective ribosomal products (DRiPs) in blebs (DRibbles) by contacting cells with a proteasome inhibitor, and in some examples also an autophagy inducer, thereby producing treated cells. DRibbles can be used to load antigen presenting cells (APCs), thereby allowing the APCs to present the DRiPs and antigenic fragments thereof. Immunogenic compositions that include treated cells, isolated DRibbles, or DRibble-loaded APCs are also disclosed. Methods are also provided for using treated cells, isolated DRibbles, or DRibble-loaded APCs to stimulate an immune response, for example in a subject. For example, DRibbles obtained from a tumor cell can be used to stimulate an immune response against the same type of tumor cells in the subject. In another example, DRibbles obtained from a pathogen-infected cell or cell engineered to express one or more antigens of a pathogen can be used to stimulate an immune response against the pathogen in the subject.

Provided herein are antibodies and chimeric priming receptors that bind PSMA and antibodies and chimeric antigen receptors that bind CA9. Also provided are systems of chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9, cells expressing such systems, and methods of use thereof.

Embodiments of the disclosure concern methods and compositions related to targeted cancer therapy directed to a particular terminal deoxynucleotidyl transferase peptide associated with HLA-A02. In specific embodiments, cellular therapy employs cells encoding a chimeric T-cell receptor that targets the peptide and optionally also a bi-specific T-cell engager that targets the same peptide. In particular embodiments, one or both are used to treat a hematological malignancy.

The present disclosure provides NK cells useful for therapy. A Natural Killer (NK)-cell includes nucleic acids for expressing an T-cell Receptor (TCR), CD3, CD3, CD3 and CD3 in its cell membrane, and a nucleic acid for expressing and secreting a bispecific protein, wherein the bispecific protein includes a first Fv for binding to a first target epitope and a second Fv for binding to a second target epitope, wherein the first Fv specifically binds, under physiological conditions, to an epitope located on the extracellular part of a CD3-chain, and wherein the second Fv specifically binds, under physiological conditions, to an epitope located on target cells.