Provided for herein are viral particles comprising a heterologous viral glycoprotein and a targeting moiety, wherein the targeting moiety comprises a polypeptide comprising a formula of T-S.sub.1, wherein T is a target binding domain and S.sub.1 is a stalk portion. The stalk portion may comprise a variant Fc domain. The stalk portion may comprise a flexible polypeptide domain. The targeting moiety comprising the formula T-S.sub.1 may be incorporated into a viral particle to assist with targeting such particles to a specific cell type. Also provided for herein are compositions comprising the same, and methods of using the same.

The present disclosure provides compositions of immune cells presenting a target molecule or a fragment thereof and provides compositions and methods of producing immune cell therapies with targeted activity against cancer. Methods for conditioning a subject receiving the immune cell therapy of the disclosure are additionally disclosed. The immune cell therapies of the present disclosure can be administered to a subject in need thereof for diseases such as cancer.

Novel therapeutic immunotherapy compositions comprising at least two vectors, each vector encoding a functional CAR, whereby the combination of vectors results in the expression of two or more non-identical binding domains, wherein each vector encoded binding domain(s) are covalently linked to a transmembrane domain and one or more non-identical intracellular signaling motifs are provided herein as well as are methods of use of same in a patient-specific immunotherapy that can be used to treat cancers and other diseases and conditions.

Disclosed are a universal CAR-T cell knocking out one or more of CD3 delta, CD3 gamma, CD3 epsilon and CD3 zeta, and simultaneously introducing the HSV-TK gene. Also disclosed are a method for preparing the above-mentioned CAR-T cell, a preparation comprising the CAR-T cell, and the use of the CAR-T cell.

The present invention provides a system for drug-inducible expression of a polynucleotide comprising a) a first nucleic acid sequence comprising a first promoter inducible by said drug, wherein the first promoter is operably linked to said polynucleotide, wherein said first promotor comprises a binding site for a DNA binding domain, wherein said binding site comprises at least one responsive element that is recognized by said DNA binding domain (DBD), and b) a second nucleic acid sequence comprising a second promoter, wherein the second promoter is operably linked to a nucleic acid sequence encoding a synthetic transcription factor, wherein said synthetic transcription factor comprises i) an activation domain (AD), wherein said AD comprises the p65 activation domain of the human transcription factor NFB or a functional variant thereof, ii) said DNA binding domain (DBD), wherein said DBD comprises or consists of 3 zinc finger domains, iii) a ligand-binding domain (LBD), wherein said LBD is a modified human estrogen receptor which is able to bind said drug, and wherein said ligand-binding domain (LBD) is positioned at the C-terminus of said synthetic transcription factor, and c) said drug, wherein said drug is tamoxifen or a metabolite of tamoxifen.

Combination therapy of a cancer with a multi-specific binding protein that bind a tumor associated antigen, the NKG2D receptor, and CD16, in combination with a second anti-cancer agent are described. Also described are pharmaceutical compositions of the multi-specific binding protein, and therapeutic methods useful for the treatment of cancer in combination with a second anti-cancer agent.

Compositions and methods for efficient cellular genomic engineering that transduce diverse cell types with minimal toxicity, leading to efficient and stable genomic modifications are described. The compositions and methods are applicable to development of chimeric antigen receptor engineered T cell therapy (CAR-T). An exemplary method introduces a gene of interest into cells by introducing to the cell a viral vector including a transposon encoding the gene of interest and mRNA including a sequence that encodes transposase enzymes configured to mediate targeted integration of the transposon into the cellular genome, whereby the mRNA is introduced to the cell via electroporation. Also disclosed are genetically modified cells and pharmaceutical compositions and methods of use thereof for treating subjects having diseases or disorders.

The present disclosure provides bispecific chimeric antigen receptors targeting CD20 and BCMA. The CAR may comprise an scFv targeting CD20 and an scFv targeting BCMA, a hinge region, a transmembrane domain, a co-stimulatory region, and a cytoplasmic signaling domain. The chimeric antigen receptors can be used to treat autoimmune disorders or cancer.

A gene using a BCMA extracellular domain as a marker, a polypeptide, a recombinant expression vector, a genetically engineered cell, and use thereof are provided. The gene tBCMA is a gene encoding a complete or partial sequence of the BCMA extracellular domain, or a gene encoding a sequence at least 85% identical to the complete or partial sequence. An extracellular domain polypeptide (tBCMA) of the B cell maturation antigen is used as a marker for the technology of detecting and removing the genetically engineered immune cells. The gene using the BCMA extracellular domain as the marker can be widely used for the detection of various genetically engineered immune cells, thereby effectively solving the problems of detection of the genetically engineered immune cells after preparation and infusion, and providing a feasible strategy when these cells need to be removed due to serious toxic and side effects in clinical therapy.

Provided for herein are mutant VSV-G polypeptides, compositions comprising the same, and methods of using the same. Also provided for herein are polypeptides and compositions that bind to CD7 and uses thereof. Also provided for herein are polypeptides and compositions that bind to CD8 and uses thereof.