The present invention relates to nucleic acid constructs and their use to develop host cell lines for production of a protein of interest, and in particular to nucleic acid constructs which allow for improved selection to develop high-producing cell lines.

The present disclosure relates to expansion and activation of T cells. In an aspect, the present disclosure relates to expansion and activation of γδ T cells that may be used for transgene expression. In another aspect, the disclosure relates to expansion and activation of γδ T cells while depleting α- and/or β-TCR positive cells. T cell populations comprising expanded γδ T cell and depleted or reduced α- and/or β-TCR positive cells are also provided for by the instant disclosure. The disclosure further provides for methods of using the disclosed T cell populations.

Compounds of formulae (I) and (II), compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo.

##STR00001##

The present disclosure relates to anti-TRBCl antigen binding domains characterized by the sequences of the variable chains. The CDRs sequences of the variable chains are: (VH CDR1) GYTFT, (VH CDR2) NPYNDDIQS, (VH CDR3) GAGY-NFDGAYRFFDF; and (VL CDR1) RSSQRLVHSNGNTYL, (VL CDR2) RVSNRFP, (VL CDR3) SQSTHVPYT. The claimed humanized antibodies derive from the murine JOVI antibody. Uses in cancer therapy.

The present invention provides isolated T cell receptors (TCRs) that specifically bind to an HLA-displayed cancer testis antigen preferentially expressed antigen in melanoma (FRAME) peptide, as well as therapeutic and diagnostic methods of using those isolated TCRs.

The present invention is directed to the field of immunotherapy, in particular, adoptive T cell therapy or T cell receptor (TCR) gene therapy of cancer. The invention provides nucleic acids encoding at least one TCR alpha or beta chain construct of a TCR construct capable of specifically binding to a peptide from the T-cell lineage specific antigen CD5, preferably SEQ ID NO: 1 or 33, in the context of a human MHC I such as HLA-A*02, in particular HLA-A*02:01. The invention also provides corresponding proteins and host cells, preferably, CD8+ T cells, expressing said TCR construct. Treatment optionally is in the context of allogeneic stem cell transplantation, in particular, mismatch-transplantation, or haploidentical transplantation, or in combination with an agent capable of inhibiting expression of HLA-A*02 in the TCR-transgenic T cells. The invention thus also provides compositions and kits comprising the nucleic acids of the invention in combination with an agent capable of inhibiting expression of HLA-A*02, and, as well as the medical use of such compositions and kits. The nucleic acids, compositions and kits, proteins or host cells may be for use in the diagnosis, prevention and/or treatment of a CD5-positive T-cell lymphoma or T-cell leukemia, no matter whether the antigen is expressed on the cell surface, intracytoplasmic or in both manners.

The present disclosure describes the fusogenic activity of the Myomaker protein. This polypeptide, when expressed in non-muscle cells, is able to drive fusion of the cell with a muscle cell, but not with other non-muscle cells. The use of this protein and cell expressing it in the delivery of exogenous genetic material to muscle cells also is described.

Methods and compositions related to type 2 diabetes therapy are described, where the methods and compositions relieve ER stress in pancreatic islet cells. The present disclosure provides methods and compositions for reducing hepatic steatosis, e.g., associated with Type 2 diabetes (T2D). In one aspect, the present disclosure provides a method of reducing hepatic steatosis, e.g., associated with T2D, in a subject in need thereof.

Provided herein are anaplastic lymphoma kinase chimeric antigen receptors (ALK CARs). The invention also provides polynucleotides encoding ALK CARs, engineered immune cells comprising an ALK CAR, pharmaceutical compositions thereof, and kits for administering the same. Methods of treating a subject with a disease by administering the ALK CAR or engineered immune cell comprising an ALK CAR, or pharmaceutical compositions thereof, are also provided.

Provided is a viral particle comprising a genomic RNA suitable for delivering a polynucleotide sequence of interest (SOI) into a cell and/or a subject. The genomic RNA comprises, from 5′ to 3′: (a) the SOI replacing the upstream R, (b) a U5, (c) a primer binding site (PBS), (d) an encapsidation signal (Psi), (e) polypurine tract(s) (PPT), and (f) a U3. The SOI preferably takes the form of single-stranded DNA or a DNA-RNA hybrid after initiation of reverse transcription. Additionally provided are polynucleotides, vectors, cells, components, compositions, kits, methods and uses of the viral particle.