Immunoresponsive cells comprising an NKG2D polypeptide and a CXCR2 polypeptide, and, optionally, a fusion polypeptide comprising a DNAX-activating 10 (DAP10) polypeptide and a DNAX-activating protein 12 (DAP12) polypeptide, are provided. Also provided are methods of making and using such immunoresponsive cells.

Disclosed herein are methods of gene editing, or endogenous suppression, of cytokines/chemokines/transcription factors secreted from chimeric antigen receptor (CAR)-bearing immune effector cell such as CAR-T cells for the mitigation of cytokine release syndrome and/or CAR-T associated neuropathy. These methods involve insertion of the CAR into a locus of a cytokine gene, blocking its expression. Also disclosed herein are (CAR)-bearing immune effector cells with CARs inserted into a locus of a cytokine gene, and methods of treatment of diseases with immunotherapy with a reduced incidence of cytokine release syndrome and/or CAR-T associated neuropathy.

A method of manufacturing of Natural Killer (NK) Cells genetically modified with lentiviral vectors carrying a polynucleotide coding for a Chimeric Antigen Receptors (CARs). CAR-NK cells obtained with the method, and the use of the CAR-NK cells in medicine, in particular for use in a method of treating cancer is also disclosed.

Provided herein, in some embodiments, are methods and compositions (e.g., cell compositions) for the treatment of cancer, such as LIV1.sup.+ malignancies.

Compositions and methods are provided to treat and prevent cancers, such as myelomas, and include adoptive cell therapies in combination with an IL-15 superagonist and one or more chemotherapeutic agents.

The present disclosure relates to modified T cell receptors and use thereof to enhance binding of the TCR to BTN3A1 or a BTN2A1/BTN3A1 complex.

The compositions and methods described herein are directed to treating solid tumor using CAR T therapy. The compositions include CAR comprising an extracellular domain that binds a siglec protein or a receptor that binds the peptide hormone kisspeptin.

The present disclosure relates to modified invariant natural killer T (INKT) cells or type I natural killer T (NKT) cells (e.g., CD3.sup.+iTCR V24-J18.sup.+ or CD3.sup.+V24.sup.+) to express a CD7 chimeric antigen receptor (CAR) as therapeutic agents for the treatment of a CD7 cancer, and pharmaceutical compositions, methods of preparation, and therapeutic uses thereof.

The invention provides binding proteins capable of specific binding to a human leukocyte antigen (HLA) complex type A2 presenting a peptide having the amino acid sequence ALYDKTKRI set forth in SEQ ID NO: 1 (peptide T1) or the amino acid sequence ALYDKTKRIFL set forth in SEQ ID NO: 15 (peptide T3) derived from human terminal deoxynucleotidyl transferase (TdT). The binding proteins comprise an antigen binding unit comprising an -chain variable domain and a -chain variable domain each comprising 3 complementarity determining regions (CDRs) derived from TCRs that recognise the peptides. The binding proteins and cells expressing them, may be used in cancer therapy.

New synthetic expression cassettes comprising a minimal promoter and a cell-specific enhancer for expression of a nucleic acid of interest in one or more specific cell subtypes are disclosed. Vectors and host cells comprising such synthetic expression cassettes are also disclosed. The application also discloses methods for expressing a nucleic acid of interest, such as a nucleic acid encoding a chimeric antigen receptor (CAR), in a cell and for treating diseases or conditions such as cancers and genetic diseases using the synthetic expression cassettes, vectors and cells.