The disclosure relates to a dual vector system with a first vector comprising a sequence encoding an inhibitory receptor and a sequence encoding a first part of an activator receptor; and a second vector, comprising a sequence encoding a second part of the activator receptor.

The present invention relates to: a novel chimeric antigen receptor containing, as an intracellular signaling domain, an intracellular domain of a receptor containing a dead region; and immune cells expressing the chimeric antigen receptor. In environments in which normal cells are present, the immune cells expressing the chimeric antigen receptor according to the present invention exhibit little or no cytotoxicity and cell death of the immune cells is exhibited, thus ensuring the stability of the normal cells. Conversely, in environments in which target cells are present, the immune cells exhibit more potent cytotoxicity than with conventional techniques utilizing a lone chimeric antigen receptor.

The technology relates in part to binding molecules that specifically bind to a polypeptide that is the Isoform 2 of mesotheiin, or that specifically bind to an antigenic determinant (epitope) of the isoform 2 of mesotheiin, or that specifically bind to polypeptides containing an antigenic determinant (epitope) of the isoform 2 of mesotheiin, chimeric PD1 receptors that bind to PD ligands such as PDLs, to polynucleotides including vectors that encode such binding molecules, to ceils presenting such binding molecules and to methods of making such cells, to humanized forms of the binding molecules, and to methods of using such binding molecules, such as for treating cancers (e.g., ovarian cancers and mesotheliomas), including cancers in which the Isoform 2 of mesotheiin is specifically expressed and/or upregulated relative to normal tissues.

The invention provides antigen binding domains that bind myeloid cell surface antigen CD33 protein comprising the antigen binding domains that bind CD33, polynucleotides encoding them, vectors, host cells, methods of making and using them.

A method efficiently produces cytotoxic T lymphocytes having intrinsic properties of lymphocytes of the acquired immune system suitable for cellular immunotherapy. The method includes culturing CD4/CD8 double-positive T cells in a medium containing IL-7 and a T-cell receptor activator, to induce CD8?.sup.+?.sup.+ cytotoxic T lymphocytes.

The present disclosure provides a TCR-T cell for tumor-killing, wherein the TCR-T cell is a T cell carrying a TCR that recognizes a tumor antigen, and the TCR in the TCR-T cell is derived from any one or more of the following T cells: 1) a CD4 T cell expressing one or more of TNFRSF18, CXCL13, TNFRSF4, TNFSF8, ENTPD1, ACP5, LAYN, TNFRSF9, CTLA4, CD200 and TIGIT genes in the tumor; and 2) a CD8 T cell expressing one or more of TNFRSF18, CXCL13, CXCR6, GALNT2, ENTPD1, ACP5, HAVCR2, LAYN, TNFRSF9, CTLA4 and CD109 genes in the tumor. The TCR-T cell according to the present disclosure can be effectively applied to the treatment of a tumor, especially in an immunotherapy.

The present invention provides compositions comprising anti-CEACAM1 antibodies, compositions comprising antibodies capable of inhibiting or blocking the interaction between PD-1 and its ligands, and methods for their combined use in treating cancer.

Provided herein are de novo binding domain containing polypeptides (DBDpp) that specifically bind a target of interest. Nucleic acids encoding the DBDpp, and vectors and host cells containing the nucleic acids are also provided. Libraries of DBDpp, methods of producing and screening such libraries and the DBDpp identified from such libraries and screens are also encompassed. Methods of making and using the DBDpp are additionally provided. Such uses include, without limitation, affinity purification, and diagnostic and therapeutic applications.

Provided herein are de novo binding domain containing polypeptides (DBDpp) that specifically bind a target of interest. Nucleic acids encoding the DBDpp, and vectors and host cells containing the nucleic acids are also provided. Libraries of DBDpp, methods of producing and screening such libraries and the DBDpp identified from such libraries and screens are also encompassed. Methods of making and using the DBDpp are additionally provided. Such uses include, without limitation, affinity purification, and diagnostic and therapeutic applications.

The present invention relates to compositions and methods of generating modified hematopoietic stem or progenitor cells. One aspect of the invention includes a modified hematopoietic stem or progenitor cell comprising a nucleic acid capable of decreasing expression of an endogenous gene or a portion thereof, wherein the endogenous gene encodes a polypeptide comprising an antigen domain targeted by a chimeric antigen receptor (CAR). Another aspect of the invention includes a method for generating a modified hematopoietic stem or progenitor cell. Also included are methods and pharmaceutical compositions comprising the modified cell for adoptive therapy and treating a condition, such as an autoimmune disease or cancer.