The present invention relates to compositions and methods that provide novel therapies in cancer. The invention includes a phagocytic cell modified with a repressor of signal regulatory protein-alpha (SIRP) and bound to a targeting antibody to enhance phagocytic activity of the phagocytic cell toward tumor tissue. Methods of enhancing phagocytic activity and treating a tumor are also included.

Engineered T cell receptor (TCR) complex and methods of using same are provided. Accordingly, there is provided a TCR comprising a TCR alpha polypeptide and a TCR beta polypeptide, wherein the TCR is devoid of a binding domain, wherein the TCR alpha and beta polypeptides comprise amino acid modifications enabling presentation of the TCR as a TCR complex on a surface of a T cell expressing same. Also provided are polynucleotides encoding the TCR. T cells expressing the TCR complex and methods of using same.

A programmable receptor complex expressed by an immunocyte, wherein the programmable receptor complex includes a plurality of native or endogenously expressed receptor subunits, wherein the native or endogenously expressed receptor subunits have been engineered or modified to include FcRI receptor components, biotin-binding components, or both, and wherein the FcRI receptor components and biotin-binding components are operative to bind to target detector molecules that bind to or otherwise interact with predetermined targets.

A chimeric antigen receptor is provided, including an extracellular segment, including a single-chain antibody region binding to an antigen human CD19 and a hinge region, a trans-membrane segment, including a trans-membrane domain of human CD8 linked to the hinge region of the extracellular segment and embedded in cell membrane of T lymphocyte, and an intracellular segment, including an intracellular domain of human CD8, an intracellular domain of molecule 4-1BB and an intracellular domain of CD3 chain. The single-chain antibody region includes a heavy-chain variable region and a light-chain variable region of the single-chain antibody, the hinge region includes an extracellular domain of human CD8 alpha (CD8) of 55 amino acid residues and three alanine residues (AAA) located at the N-terminal of the extracellular domain of human CD8, and the intracellular domain of human CD8 includes seven amino acid residues and linked to the trans-membrane domain of human CD8.

The present disclosure provides nucleic acid constructs for the treatment of cancer, comprising a cancer-specific promoter and one or more therapeutic genes.

The present disclosure provides improved genome editing compositions and methods for editing a CBLB gene. The disclosure further provides genome edited cells for the prevention, treatment, or amelioration of at least one symptom of, a cancer, an infectious disease, an autoimmune disease, an inflammatory disease, or an immunodeficiency.

Provided herein are constitutively active chimeric cytokine receptors (CACCRs). When present on chimeric antigen receptor (CAR)-bearing immune cells, such CACCRs allow for increased immune cell activation, proliferation, persistence, and/or potency. Also provided are methods of making and using the CACCRs described herein.

A fully human antibody targeting GPRC5D and a chimeric antigen receptor (CAR) comprising the fully human antibody. A host cell expressing the CAR, such as a CAR-T cell. A use of the fully human antibody, the CAR, and the CAR-T cell in treatment of tumors (such as multiple myeloma).

Embodiments described herein relate to methods, devices, and computer systems thereof for the derivation of T CAR libraries (Universal Subject or Individual Subject) for personalized treatment of disease in a subject. In certain embodiments, differential screening of normal and diseased tissue expression data is utilized to determine disease-specific antigens and thereby generate T CAR cells reactive to such antigens to form a disease-specific library. In certain embodiments, determination of the most effective T CAR clones from the disease-specific library is based on the subject's own disease-specific antigens. In certain embodiments, a subject is treated with a therapeutically effective amount of T CAR clones.

The present invention relates to a composition for expanding lymphocytes comprising at least two types of cytokines selected from interleukin 2 (IL-2), interleukin 15 (IL-15) and interleukin 21 (IL-21). It further relates to a Method of preparing a population of clinically relevant lymphocytes, comprising the steps of: obtaining a body sample from a mammal in particular a tissue sample or body liquid sample, comprising at least one lymphocyte and optionally separating the cells in the body sample, culturing the body sample in-vitro to expand and/or stimulate lymphocytes in the sample wherein the culturing comprises using IL-2, IL-15 and/or IL-21, and optionally determining the presence of clinically relevant lymphocyte in the cultured sample. The present invention also relates to an immunotherapy and the population of clinically relevant lymphocytes.