The present invention relates to, inter alia, compositions and methods, including engineered T cells that express chimeric antigen receptors and heterologous chimeric proteins that find use in the treatment of cancer.

An immunoresponsive cell, such as a T-cell expressing (i) a second generation chimeric antigen receptor comprising: (a) a signalling region; (b) a co-stimulatory signalling region; (c) a transmembrane domain; and (d) a binding element that specifically interacts with a first epitope on a target antigen; and (ii) a chimeric costimulatory receptor comprising (e) a co-stimulatory signalling region which is different to that of (b); (f) a transmembrane domain; and g) a binding element that specifically interacts with a second epitope on a target antigen.

This arrangement is referred to as parallel chimeric activating receptors (pCAR). Cells of this type are useful in therapy, and kits and methods for using them as well as methods for preparing them are described and claimed.

An inducible chimeric antigen receptor and its application relate to the field of immune therapy. The inducible antigen receptor includes a single-chain variable fragment (scFv) antibody against human CSF1R, a truncated hIgG1 hinge region SH, a T cell co-stimulatory signaling molecule, and a T cell cytoplasmic signaling domain. Transcription of the chimeric antigen receptor is regulated by an inducible expression element tet operator. The induce chimeric antigen receptor molecules can be used to modify T lymphocytes, eliminating the cytokine storm problem of CAR-T cells in the treatment of Alzheimer's disease (AD), and achieving target treatment of AD.

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.

Described herein are methods and compositions for selective activation of cells using variant cytokine receptor and cytokine pairs, wherein the cytokine receptors comprise an extracellular domain (ECD) of granulocyte-colony stimulating factor receptor (G-CSFR). In certain embodiments, the methods and compositions described herein are useful for exclusive activation of cells for adoptive cell transfer therapy. Thus, included herein are methods of producing cells expressing variant receptors that are selectively activated by a cytokine that does not bind its native receptor. Also disclosed herein are methods of treating a subject in need thereof, comprising administering to the subject cells expressing an variant receptor comprising an extracellular domain of G-CSFR and co-administering a variant cytokine that activates the variant receptor.

The disclosure provides compositions and methods for cell therapy of hPAP in humans using gene corrected and in vitro differentiated patient autologous macrophage cells. The disclosure also provides compositions in the form of a cell product and related compositions and methods for making the cell product and for direct pulmonary transplantation of same.

An immunoresponsive cell, such as a T-cell expressing a second generation chimeric antigen receptor comprising: (a) a signalling region; (b) a co-stimulatory signalling region; (c) a transmembrane domain; and (d) a binding element that specifically interacts with a first epitope on a target antigen; and a chimeric costimulatory receptor comprising (e) a co-stimulatory signalling region which is different to that of (b); (f) a transmembrane domain; and g) a binding element that specifically interacts with a second epitope on a target antigen.

This arrangement is referred to as parallel chimeric activating receptors (pCAR). Cells of this type are useful in therapy, and kits and methods for using them as well as methods for preparing them are described and claimed.

An immunoresponsive cell, such as a T-cell expressing (i) a second generation chimeric antigen receptor comprising: (a) a signalling region; (b) a co-stimulatory signalling region; (c) a transmembrane domain; and (d) a binding element that specifically interacts with a first epitope on a target antigen; and (ii) a chimeric costimulatory receptor comprising (e) a co-stimulatory signalling region which is different to that of (b); (f) a transmembrane domain; and (g) a binding element that specifically interacts with a second epitope on a target antigen.

This arrangement is referred to as parallel chimeric activating receptors (pCAR). Cells of this type are useful in therapy, and kits and methods for using them as well as methods for preparing them are described and claimed.

The present invention relates to the recognition of CSF1R as a marker of hematological cancer and thus relates to CSF1R targeting agents for the treatment of such cancers, in particular, AML. The invention also relates to a lymphocyte recombinantly expressing a chimeric antigen T cell receptor (CAR) specific for CSF1R, in particular, for use in the treatment of cancer characterized by the expression of colony stimulating factor 1 receptor (CSF1R). The present invention further relates to a CAR comprising an extracellular domain that specifically binds CSF1R, a transmembrane domain, and an intracellular T cell activating domain; as well as polynucleotides, vectors and host cells used in the production of the CAR. Further, methods for the production of such lymphocytes and a pharmaceutical composition comprising such lymphocytes are provided. The cells of the invention are preferably human lymphocytes and more preferably primary human lymphocytes such as CD3+ T cells, CD8+ T cells, CD4+ T cells, ?? T cells, invariant T cells or NK T cells.