The invention provides compositions and methods for treating diseases associated with expression of CD123. The invention also relates to chimeric antigen receptor (CAR) specific to CD123, vectors encoding the same, and recombinant cells comprising the CD123 CAR. The invention also includes methods of administering a genetically modified cell expressing a CAR that comprises a CD123 binding domain.

The HIV-specific cytotoxic T lymphocyte (CTL) response is a critical component in controlling HIV replication and is an important part of the ultimate failure to eradicate the virus. Disclosed herein are methods for genetically enhancing the HIV-specific CTL response to allow long-term viral suppression or viral clearance. Human hematopoietic stem cells (HSCs) were genetically modified such that they differentiate into mature CTLs that will kill HIV infected cells. As disclosed herein, the functional effector cells are not human leukocyte antigen (HLA)-restricted. As disclosed herein, stem cells are transduced with non-HLA restricted chimeric antigen receptors (CARs) that allow the recognition of HIV or HIV-infected cells when expressed by a CTL. These CARs are hybrid molecules that contain an extracellular HIV recognition domain and an intracellular TCR-zeta signaling domain. The CTL response may be enhanced through the targeting of T cell inhibitory receptors. The methods and compositions disclosed herein may be used to engineer antiviral immunity and HIV-specific CTL responses in vivo. Also disclosed herein are methods and compositions for the treatment of chronic viral infections such as HIV.

Provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing an inducible pattern recognition receptor adapter, or adapter fragment, and CD40 activity. Also provided are nucleic acid compositions comprising sequences coding for chimeric proteins that include an inducible CD40 peptide and an inducible pattern recognition receptor adapter or adapter fragment.

Chimeric antigen receptors containing tumor necrosis factor receptor superfamily member transmembrane domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

The present disclosure provides a heterodimeric, conditionally active chimeric antigen receptor (CAR), and a nucleic acid comprising a nucleotide sequence encoding the CAR. The present disclosure provides cells genetically modified to produce the CAR. A CAR of the present disclosure can be used in various methods, which are also provided.

The invention relates to an peptide derived from a polymorphic region of donor MHC class II molecules which induces tolerance and thus prevents transplant rejection in a patient in need thereof. The invention relates to an isolated peptide of 15 or 16 amino acids long that comprises or consists of the amino acid sequence: REEYARFDSDVGEYR (SEQ ID NO: 1) or a function-conservative variant for use as drug. The invention relates to an in vitro method for determining whether a transplanted patient is tolerant, comprising a step of determining the presence of CD8.sup.+CD45RC.sup.low Tregs in a biological sample obtained from said transplanted patient, wherein the presence of CD8.sup.+CD45RC.sup.low Tregs is indicative of tolerance.

The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

The invention provides compositions and methods for treating diseases associated with expression of a cancer associated antigen as described herein. The invention also relates to chimeric antigen receptor (CAR) specific to a cancer associated antigen as described herein, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to a cancer associated antigen as described herein.

The present invention relates to therapeutic and prophylactic methods based on inhibition of CIS in NK cells. In particular, the present invention relates to treating or preventing a NK-responsive condition by administering to a subject a CIS inhibitor, or administering CIS-inhibited NK cells. The invention further relates to methods for identifying a CIS inhibitor, and for determining a likelihood of cancer response to treatment with CIS inhibition.

The present invention relates to the discovery that increases in invariant NKT cell (iNKT) number and/or activity can reduce the incidence or severity of metabolic disorders such as obesity and diabetes. The invention accordingly features methods, kits, and compositions for the treatment of such metabolic disorders by administration of a composition capable of increasing iNKT activity.