The present application relates to a chimeric antigen receptor (CAR) which comprises a target-dependent on-switch CAR. The CAR of the invention may reduce cytotoxicity towards normal cells and improve CAR-T safety. CAR molecules were designed using the transmembrane and juxtamembrane motifs of the IL2 receptor β chain (IL2Rβ or IL2Rb), the L ow-Density Lipoprotein Receptor (LDLR), the Seizure 6-like Protein 2 (SEZ6L2), and degradation sequence (PSKFFSQL) of IL2Rβ, which resulted in greatly reduced CAR expression at the cell surface in the absence of target antigen, while retaining downstream activation ability in response to antigen-expressing target cells. In the absence of target antigen, CAR surface expression is undetectable. The present application has shown that primary T cells expressing these surface-unstable CAR variants are able to elicit antigen-dependent target cell killing. By limiting CAR activity in this way, the present application can reduce therapeutic toxicity and T cell exhaustion. Due to its limited detectability in the absence of antigen, the present application refers to this system as a “Stealth CAR”. The present application further relates to compositions, preparation methods and uses of the Stealth CAR of the present application.

Methods for treating a CD30-positive cancer in a subject are disclosed, wherein the methods comprise administering a lymphodepleting chemotherapy and CD30-specific chimeric antigen receptor (CAR)-expressing cells.

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.

The present invention relates to a polypeptide encoding a SLAMF7-binding chimeric antigen receptor (CAR), a polynucleotide encoding the SLAMF7-binding CAR polypeptide, a recombinant immune cell (preferably recombinant lymphocyte, more preferably recombinant T cell) comprising the polynucleotide, a method for producing recombinant immune cells and a pharmaceutical composition comprising recombinant immune cells. The recombinant immune cells and the pharmaceutical composition of the present invention may be used in methods for treating cancer in a patient thereby providing an improved treatment regimen. The inventors of the present application demonstrated that SLAMF7 CAR T-cells prepared by Sleeping Beauty gene transfer confer superior anti-myeloma efficacy in vivo compared to SLAMF7 CAR T-cells prepared by lentiviral gene transfer. Hence, SLAMF7 CAR T-cells that are prepared by virus-free SB gene transfer possess greater anti-myeloma efficacy and therapeutic potential, which leads to significantly improved clinical activity, and significantly improved clinical outcome.

A population of genetically engineered T cells, comprising a nucleic acid encoding an anti-CD83 CAR, a disrupted Reg1 gene, and/or a disrupted TGFBRII gene. Such genetically engineered T cells may comprise further genetic modifications, for example, a disrupted CD83 gene. The population of genetically engineered T cells exhibit one or more of (a) improved cell growth activity; (b) enhanced persistence; and (c) reduced T cell exhaustion, (d) enhanced cytotoxicity activity, (e) resistant to inhibitory effects induced by TGF-β, and (f) resistant to inhibitory effects by fibroblasts and/or inhibitory factors secreted thereby, as compared to non-engineered T cell counterparts.

Provided herein is a chimeric antigen receptor (CAR) and CAR-expressing immune cells that target human RORI expressed aberrantly on a tumor cancers. Described herein are chimeric antigen receptors that target human ROR-1, cell compositions expressing the chimeric antigen receptors, and methods and uses of the chimeric antigen receptors and/or the cell compositions. The chimeric antigen receptors described herein can be expressed by the T lymphocytes isolated from an individual afflicted with cancer and re-administered to the individual.

The present invention inter alia relates to a method of selecting a patient for treatment of a solid tumor, wherein cells of the tumor express the human melanoma associated antigen 1, to a method of predicting whether a patient being diagnosed with a MAGE-1A positive solid tumor will be responsive to treatment of this tumor as well as to methods of treating a patient being diagnosed with a MAGE-1A solid tumor. The invention also relates to a pharmaceutical composition comprising T cells expressing a T cell receptor that specifically binds MAGE-1A and to a diagnostic immunostaining kit for selecting a patient for treatment of a solid tumor.

The present disclosure provides an anti-EpoR peptide for use in the treatment of a disease such as cancer. In the description, a peptide which has the structure: -[SCHFGPLTWVCK]- and which is intended to be used for antagonizing an Epo heteroreceptor selectively in the presence of erythropoietin (Epo) or an equivalent thereof, a modified peptide of the peptide, a prodrug of the modified peptide, or a salt of the peptide, the modified peptide or the prodrug (wherein, in the formula, an alphabetical letter represents a one-letter code for an amino acid residue) is provided. In one embodiment, a disease, a disorder or a symptom each characterized by the occurrence of a cell expressing an Epo heteroreceptor is treated or prevented.

Described herein are immune cells comprising: a T-cell receptor (TCR) and a chimeric stimulating receptor (CSR) that comprises (i) a ligand-binding module that is capable of binding or interacting with a target ligand; (ii) a transmembrane domain; and (iii) a CD30 costimulatory domain, in which the CSR in the immune cells lacks a functional primary signaling domain. Also provided herein are methods of using the same or components thereof (e.g., the CSR) for therapeutic treatment of cancers (e.g., solid tumor cancers).

The present invention provides methods for preselecting TILs based on PD-1, CD39, CD38, CD103, CD101, LAG3, TIM3 and/or TIGIT expression, as well as methods for expanding those preselected PD-1, CD39, CD38, CD103, CD101, LAG3, TIM3 and/or TIGIT positive TILs in order to produce therapeutic populations of TILs with enhanced tumor-specific killing capacity (e.g., enhanced cytotoxicity).