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.

The present invention refers to a novel combination of nucleotide and cellular vaccine composition and pharmaceutical composition and use thereof for treating and/or preventing diseases, including infectious diseases, cancer, autoimmune diseases, allergy, diabetes and blood disorders. The vaccine composition comprises a nucleotide sequence encoding an antigenic molecule and gene-modified antigen-presenting cells (APCs), preferably provided as an intermixture. The APCs are modified to express immune modulating molecules. Immunization with the vaccine composition of present invention into a subject, induces the host immune system to respond and generate efficient immunity against either pre-existing disease or protect the host against the disease.

The present application relates to functionally improved third generation BCMA-CARs comprising modified intracellular co-stimulatory domains, which can be used in adoptive cell therapy, e.g., in treatment of diseases and disorders such as cancer.

An engineered immune cell comprising a first functional exogenous receptor capable of binding and depleting natural killer (NK) cells, and a second functional exogenous receptor, wherein the engineered immune cell has reduced MHC I on cell surface.

A recombinant nucleic acid expression construct including a first nucleic acid sequence region encoding a chimeric antigen receptor (CAR), a second nucleic acid sequence region encoding a checkpoint inhibitory molecule, and a third nucleic acid sequence region encoding an immune stimulatory cytokine. A recombinant nucleic acid expression construct encoding the CAR specifically recognizes CD44v6, and includes a PD1 checkpoint inhibitory molecule, and an immune stimulating cytokine. Further aspects relate to genetically modified cells, including a recombinant nucleic acid expression construct encoding the CAR, wherein the cells are preferably immune cells, more preferably NK cells or cytotoxic T lymphocytes or T helper cells. Medical use of the cells may be in the treatment of a medical disorder associated with the presence of pathogenic cells expressing CD44v6, preferably cancer cells, more preferably cancer stem cells of solid or liquid malignancies.

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.

Provided herein are uses of chimeric antigen receptors (CARs) for treating a cancer (such as B cell related cancer, e.g., multiple myeloma).

Provided herein are gRNA comprising a targeting domain that targets CD7, which may be used, for example, to make modifications in cells. Also provided herein are methods of genetically engineered cell having a modification (e.g., insertion or deletion) in the CD7 gene and methods involving administering such genetically engineered cells to a subject, such as a subject having a hematopoietic malignancy.

Provided are methods, kits and compositions related to toxicity associated with administration of cell therapy for the treatment of diseases or conditions, e.g., cancer, including methods for use in predicting and treating a toxicity. In some embodiments, the toxicity is a neurotoxicity or cytokine release syndrome (CRS), such as a severe neurotoxicity or a severe CRS. The methods generally involve detecting a parameter of a biomarker or individually a parameter of each biomarker in a panel of biomarkers, such as a concentration, amount or activity, and comparing the detected parameter to a reference value for the parameter to determine if the subject is at risk for developing the toxicity, such as neurotoxicity or CRS or severe neurotoxicity or severe CRS. In some embodiments, the methods further involve administering an agent or therapy for treating, ameliorating, preventing, delaying and/or attenuating the development of the toxicity, such as neurotoxicity or CRS, such as severe neurotoxicity or severe CRS.