The invention provides improved compositions and methods for the treatment of solid cancers.

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

Provided herein is a serum-free media for culturing, such as cultivating, preparing and/or producing cells, such as immune cells, such as genetically engineered cells. Also provided is a liquid basal media and frozen supplements that can be used to produce serum-free media. The provided embodiments include methods for producing serum-free media and methods for culturing cells, such as activating, transducing, cultivating or expanded cells, in the presence of serum-free media.

A population of genetically engineered T cells, comprising a disrupted protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene and optionally a disrupted TRAC gene, a disrupted 2M gene, and/or a disrupted CD70 gene. Also provided herein are methods for making such genetically engineered T cells and therapeutic uses thereof.

The present invention is directed to a humanized BCMA single-chain variable fragment (scFv), comprising V.sub.H having the amino acid sequence of SEQ ID NO: 4 and V.sub.L having the amino acid sequence of SEQ ID NO: 5. The present invention is also directed to a BCMA chimeric antigen receptor fusion protein comprising from N-terminus to C-terminus: (i) a single-chain variable fragment (scFv) of the present invention, (ii) a transmembrane domain, (iii) at least one co-stimulatory domains, and (iv) an activating domain. This humanized BCMA-CAR-T cells have specific killing activity with secretion of cytokine IFN-gamma in CAR-T cells in vitro and in vivo.

Provided are a chimeric antigen receptor T lymphocyte for treating tumors, a preparation method therefor, and the use thereof. The chimeric antigen receptor successively comprises a single-chain antibody against a tumor cell surface antigen, a human hinge transmembrane region, a human intracellular signal domain, a self-cleaving peptide, and the full length of human CD27. The human intracellular signal domain comprises a human intracellular co-stimulatory signal domain and a human intracellular signaling domain. The method for preparing the chimeric antigen receptor T lymphocyte comprises the following steps: introducing the coding gene of the above-mentioned chimeric antigen receptor into a T cell and expressing the coding gene, thereby obtaining the CAR-T cell.

The technology relates generally to the field of immunology and relates in part to compositions and methods for growing and storing modified natural killer cells, including for example, conditional chemical regulation of natural killer cell function. The technology further relates to pharmaceutical compositions and treatment of subjects using modified natural killer cells.

Provided herein are methods of treating cancer in a subject in need thereof by administering an anti-BCMA CAR-T cell and a GPRC5DCD3 bispecific antibody. In some embodiments, the subject has relapsed and/or refractory multiple myeloma. In some embodiments, the subject has received at least one prior line of therapy. In some embodiments, the subject has newly diagnosed multiple myeloma and is transplant ineligible.

The invention provides chimeric antigen receptors (CARs), nucleic acid sequences encoding a CAR, vectors comprising a nucleic acid sequence encoding a CAR, cells expressing a CAR, pharmaceutical compositions comprising a cell expressing a CAR, wherein the CAR binds to a target molecule expressed on disease-associated macrophages (DAMs) or over- or aberrantly-expressed in fibrosis. The invention further provides vectors encoding a CAR and a fibrotic disease-modulatory molecule (FDMM), and cells expressing both a CAR and an FDMM. The invention also provides methods of treating a subject using a CAR, a nucleic acid sequence, a vector or vectors, or a CAR-expressing cell, a cell expressing both a CAR and an FDMM, or a pharmaceutical composition, and to methods of generating a CAR-expressing cell or a cell expressing both a CAR and an FDMM. The invention also provides methods of treating diseases, fibrotic conditions, inflammatory conditions, autoimmune conditions, and conditions associated with DAMs.

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