An embodiment of the invention provides a chimeric antigen receptor (CAR) comprising an antigen binding domain specific for FLT3, a transmembrane domain, and an intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of a proliferative disorder, e.g., cancer, in a mammal and methods of treating or preventing a proliferative disorder, e.g., cancer, in a mammal are also disclosed.

The present invention provides methods for inducing tolerance and/or suppressing an immune response to an antigen by passing a cell suspension containing an anucleate cell through a constriction, wherein the constriction deforms the cell thereby causing a perturbation of the cell such that an antigen and/or tolerogenic factor enters the cell. In some embodiments, the anucleate cell is delivered to an individual and the antigen is delivered to and processed in a tolerogenic environment to induce tolerance and/or suppress an immune response to the antigen.

Targeted therapeutics for the treatment of cancers expressing FOLR1, MEGF10, HPSE2, KLRF2, PCDH19, and/or FRAS1 are described. The targeted therapeutics can include a chimeric antigen receptor (CAR) expressed by an immune cell or an antibody-targeted therapeutic. The targeted therapeutics can be used to treat a variety of cancers including solid tumors and blood cancers, such as CBFA2T3-GLIS2 acute myeloid leukemia (C/G AML).

Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.

Nucleic acid constructs, vectors, and recombinant cells harboring the nucleic acid constructs or vectors are disclosed. The nucleic acid constructs include genes encoding a chimeric antigen receptor (CAR) and/or one or more transcription factors, optionally mutated. The transcription factors include those that mediate proinflammatory cytokine expression, e.g., T-bet, STAT1, or STAT4. Methods are disclosed of co-expression of the CAR and the transcription factor in a human or non-human immune cell, preferably human T cells. Also disclosed are methods for using these cells for immunotherapy, e.g., in treating cancer, infection, autoimmunity, allergy or inflammation diseases by the administration of a prophylactically or therapeutically effective amount of one or more of the nucleic acid constructs, vectors, and/or immune cells, e.g., human CAR-T cells, described herein.

The present disclosure provides compositions and methods directed to logic gated CAR-T therapies for treating cancer, such as DIPG, Ewing Sarcoma, and AML, including logic pairs of CAR polypeptides comprising anti-CD56 CAR polypeptides and anti-CD99 CAR polypeptides.

The present disclosure provides compositions and methods directed to logic gated CAR-T therapies for treating cancer, such as DIPG, Ewing Sarcoma, and AML, including logic pairs of CAR polypeptides comprising anti-CD276 CAR polypeptides and anti-CD99 CAR polypeptides.

The present disclosure relates to a chimeric antigen receptor (CAR) which comprises an antigen-binding domain which selectively binds TCR beta constant region 1 (TRBC1) or TRBC2; cells; such a T cells comprising such a CAR; and the use of such cells for the treatment of a T-cell lymphoma or leukaemia in a subject.

The present invention relates to a peptide compound of PDL2 selected from a peptide fragment, a functional homologue, and a functional analogue, as well as to a nucleic acid, such as DNA or RNA, encoding the peptide compound, a vector, such as a virus vector, and a host cell, such as mammalian cell, comprising the vector. The peptide compound, nucleic acid, vector and host cell of the present invention are in particular, useful for the treatment or prevention of a cancer characterized by expression of PDL2.

Disclosed herein are genome editing systems and related methods which allow for treatment of Hyper IgM Syndrome, a group of disorders characterized by defective CD40 signaling. The compositions and methods described herein rely on the use of donor templates comprising a CD40L exons to restore proper CD40 signaling and B cell class switch recombination.