A population of immune cells comprising modified immune cells with reduced inflammatory properties, wherein such modified immune cells may have reduced production of one or more inflammatory cytokines (e.g., interleukin 2) and/or express one or more antagonists of one or more inflammatory cytokines (e.g., interleukin 6). Also provided herein are methods of producing such immune cell populations comprising the modified immune cells and methods of using such in cell therapy (e.g., to treat cancer, infectious diseases or immune diseases).

Described herein are chimeric receptors comprising G-CSFR extracellular domains and the intracellular domains of various multi-subunit cytokine receptors for selective activation of cytokine signaling in cells of interest. In certain aspects, the selective activation of cytokine signaling in cells expressing the chimeric receptors described herein includes the ability to specifically stimulate adoptively transferred cells.

The present disclosure provides improved compositions for adoptive T cell therapies for treating, preventing, or ameliorating at least one symptom of a cancer, infectious disease, autoimmune disease, inflammatory disease, and immunodeficiency, or condition associated therewith.

Nucleic acids that encode chemically-inducible fusion proteins, vectors that contain nucleic acids that encode chemically-inducible fusion proteins, chemically-inducible fusion proteins, chemically-inducible fusion protein complexes, and non-natural cells that are modified to express chemically-inducible fusion proteins to spatially and temporally control immune cell signal initiation and downstream responses for treating disease.

Provided here are compositions comprising engineered lymphocytes that secrete bispecific engager molecules, thereby activating T cells in the local environment to kill target cells. In particular embodiments, engineered lymphocytes selectively target CLL-1 positive leukemic cells, both directly and through activation of a subject's own T cells, while sparing CLL-1 negative cells, such as myeloid progenitor cells. In particular embodiments, engineered lymphocytes selectively target CD123 and CLL-1 positive leukemic cells, both directly and through activation of native T cells.

Provided are specific binding molecules, or fragments thereof, that bind to an epitope of IL13R2, a receptor polypeptide preferentially found on the surface of cancer cells rather than healthy cells. Exemplary specific binding molecules are bispecific binding molecules that comprise a fragment of an IL13R2 binding molecule and a peptide providing a second function providing a signaling function of the signaling domain of a T cell signaling protein, a peptide modulator of T cell activation, or an enzymatic component of a labeling system. Also provided are polynucleotides encoding such a specific binding molecule (e.g., bispecific binding molecule), vectors, host cells, pharmaceutical compositions and methods of preventing, treating or ameliorating a symptom associated with a cancer disease such as a solid tumor disease (e.g., glioblastoma multiforme).

The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease.

The invention provides compositions and methods for treating diseases associated with expression of CD19, e.g., by administering a recombinant T cell comprising the CD19 CAR as described herein, in combination with one or more B-cell inhibitors, e.g., inhibitors of one or more of CD10, CD20, CD22, CD34, CD123, FLT-3, ROR1, CD79b, CD179b, or CD79a. The disclosure additionally features novel antigen binding domains and CAR molecules directed to CD20 and CD22, and uses, e.g., as monotherapies or in combination therapies. The invention also provides kits and compositions described herein.

The present invention relates to gene editing methods to engineer primary immune cells that are made resistant to proteasome inhibitors, such as Bortezomib, Carfilzomib, Ixazomib, Marizomib, Delanzomib or Oporozomib, for their use in cell immunotherapy in combination with proteasome inhibitor treatments.

An IL6R block CAR-T transgenic vector for alleviating CRS includes: AmpR sequence containing ampicillin resistance gene (SEQ ID NO: 1); prokaryotic replicon pUC Ori sequence (SEQ ID NO: 2); virus replicon SV40 Ori sequence (SEQ ID NO: 3); eWPRE enhanced posttranscriptional regulatory element of hepatitis B virus (SEQ ID NO: 11); human EF1a promoter (SEQ ID NO: 12); lentiviral packaging cis-elements for lentiviral packaging; humanized single-chain antibody fragment IL6RscFv1 (SEQ ID NO: 21), IL6RscFv2 (SEQ ID NO: 22), or IL6RscFv3 (SEQ ID NO: 23) of human IL6R; IRES ribosome binding sequence (SEQ ID NO: 25); IL6 signal peptide (SEQ ID NO: 26); human antibody Fc segment (SEQ ID NO: 27); and chimeric antigen receptors of the second or third generation CAR for integrating recognition, transmission and initiation. A preparation method of the IL6R block CAR-T transgenic vector and an application thereof in a preparation of drugs for alleviating CRS.