In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

This document provides isolated immune cells that include an exogenous T cell receptor (TCR) having affinity for a splicing factor 3B subunit 1A (SF3B1) peptide as well as methods and materials for making such immune cells. For example, isolated immune cells that included an exogenous TCR having affinity for a mutant SF3B1 peptide, methods and materials for making such immune cells, and methods and materials for using such immune cells to treat mammals (e.g., a human having cancer) are provided.

Described herein are methods for identification of peptides that bind MHC-I molecules from within a starting pool of candidate epitope peptides, using a cell-based genetic immunopeptidomic screen.

The present invention provides a method of identifying the strength of one or more unique regulatory elements (URE) having conformational effect on a transcribable reporter sequence.

The present invention relates generally to immunization and immunotherapy for the treatment or prevention of HIV. In particular, the methods include in vivo and/or ex vivo enrichment of HIV-specific CD4+ T cells.

Recombinant vectors containing at least: a backbone comprising essential sequences for integration into a target cell genome; a nucleic acid encoding a CCR5 RNAi operatively linked to a a first expression control element that regulates expression of the nucleic acid encoding the RNAi of the CCR5; a nucleic acid encoding at least the extracellular domain of CD25 operatively linked to a second expression control element that regulates expression of the nucleic acid encoding at least the extracellular domain of CD25 are provided by this disclosure. In an alternative aspect, the vector also contains polynucleotides encoding TRIM5alpha and HIV TAR decoy sequences along with gene expression regulation elements such as promoters operatively linked to the polynucleotides. The vectors are combined with packaging plasmid and envelope plasmids and optionally conjugated to cell-specific targeting antibodies. Diagnostic and therapeutic methods for using the compositions are further provided herein.

A chimeric antigen receptor (CAR) cell library is established through the fusion of a cell and a vector assembly. The vector assembly carries three genetic elements corresponding to a plurality of first genetic elements encoding one or more idiotype CARs, a second genetic element carrying one or more genetic circuits, and a third genetic element encoding one or more inducible proteins, respectively. The one or more genetic circuits are pre-programmed and are each a combination of a cis-regulatory factor and a transcription factor; and the one or more inducible proteins include one or two selected from the group consisting of a drug resistance protein and a suicide protein. By designing a CAR library-genetic circuit-inducible protein coupling scheme, the cell library construction and screening for complex and unknown disease target antigens are realized, such as to solve the problems that there are complex, diverse, and variable antigens.

A modified U1 snRNA, wherein said modified U1 snRNA has been modified to bind to a nucleotide sequence within the packaging region of a lentiviral vector genome sequence.

Provided herein are methods for transduction of T cells. In some embodiments, the provided methods include transduction of T cells by incubation with a retroviral vector particle, e.g., lentiviral vector, in which the cells have been selected for CCR7+ expression. The provided methods improve the process for genetically engineering T cells by increasing transduction frequency and/or by reducing the variability in transduction frequency among biological samples. Also provided are resulting cells transduced with a recombinant or heterologous gene, and compositions thereof. In some embodiments, the provided cells and compositions can be used in methods of adoptive immunotherapy

The present disclosure features methods and compositions for expressing transgenes in microglia. The disclosed compositions comprise isolated fragments of human and murine translocator protein (TSPO) promoters and expression cassettes comprising the same. The methods involve using these promoters and/or expression cassettes to express transgenes in a cell.