Provided herein are inhibitory chimeric antigen receptor compositions and cells comprising such compositions. Also provided are methods of using inhibitory chimeric antigen receptors and cells.

The present invention relates to a method for inducing an immune response in a human or animal subject, as well as to a pharmaceutical composition for inducing an immune response, furthermore to a method for producing the pharmaceutical composition in vitro and the use of cytotoxic CD8+ T-lymphocytes activated to recognize an antigenic peptide in a pharmaceutical composition or in a method for inducing an immune response.

The invention relates to therapeutic compositions for allogeneic cellular therapy comprising TCR deficient T-cells, which are genetically engineered to express immune cell engagers, and methods related thereto.

Provided is a bispecific chimeric antigen receptor targeting CD19 and CD22, which comprises extracellular antigen binding domains of heavy-chain variable regions and light-chain variable regions of anti-CD19 and anti-CD22 antibodies. Further provided is a bispecific CAR-T cell targeting CD19 and CD22.

Compositions and methods for cellular genome engineering that permit simple and efficient targeted knock-in of a CAR and simultaneous knockout of individual genes are described. The compositions and methods are especially applicable to massively parallel engineering, selection, and identification of CAR T cell variants exhibiting a desired phenotype. AAV vectors containing crRNA and CAR expression cassettes and homology arms for targeted genomic integration thereof are provided. Also provided are libraries containing a plurality of AAV vectors and methods of use thereof in screens for identifying desirable CAR T cell variants. Methods of treatment using CAR T cell variants exhibiting improvements in one or more phenotypes are also provided.

A method for fabricating a cryomicroneedle, includes the steps of: providing a microneedle scaffold including a plurality of pores; providing a suspension including a biological agent; loading the biological agent into the microneedle scaffold by immersing the microneedle scaffold in the suspension to form a loaded microneedle scaffold; and freezing the loaded microneedle scaffold to provide the cryomicroneedle. A cryomicroneedle prepared according to the method above and methods for using such a cryomicroneedle are described as well.

The present invention generally relates to antigen binding receptors capable of specific binding to an Fc domain comprising the amino acid mutation P329G according to EU numbering. The present invention also relates to T cells, transduced with a antigen binding receptor which is recruited by specifically binding to/interacting with the mutated Fc domain of therapeutic antibodies. Furthermore, the invention relates to a kit comprising the transduced T cells of the invention and/or nucleic acid molecules, vectors encoding the antigen binding receptors of the present invention and tumor targeting antibodies comprising a mutated Fc domain.

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.

Herein, we provide genetically engineered immune effector cells, among other cells, which express CAR and secret a bispecific “trap” protein co-targeting a checkpoint protein and TGF-β or TGF-β receptor, so as to improve the antitumor immunity of the immune effector cells. Compared with conventional CAR-T cells and CAR-T cells secreting a polypeptide checkpoint inhibitor, the provided genetically engineered immune effector cells CAR-T cells with “trap” protein secretion attenuate inhibitory T cell signaling, enhance T cell persistence and expansion, and improve effector functionalities and resistance to exhaustion. In a xenograft mouse model, CAR-T cells with “trap” protein secretion significantly enhanced antitumor immunity and efficacy. Methods of using these genetically engineered cells, as well as using polynucleotides encoding the CAR and the “trap” protein, are also provided, for example, as a therapy against solid tumors.

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).