The disclosure relates to methods and materials for treating cancer. For example, recombinant vaccinia viruses having the ability to direct the expression of membrane-bound IL-12 polypeptides on the surface of infected cells and methods for using such recombinant vaccinia viruses to treat cancer are provided. Specifically, the disclosure provides a recombinant vaccinia virus comprising a vaccinia virus genome comprising a nucleic acid encoding an IL-12p35 polypeptide sequence and an IL-12p40 polypeptide sequence, wherein one of the polypeptide sequences comprises a membrane anchoring polypeptide sequence.

The present disclosure provides methods and compositions for genetically modifying lymphocytes, for example T cells and/or NK cells. In some embodiments, the methods include reaction mixtures, and resulting cell formulations, that are created using whole blood, or a component thereof that is not a PBMC, and additionally comprise T cells and recombinant retroviral particles having polynucleotides that encode a CAR. In some embodiments, modified lymphocytes are reintroduced into a subject subcutaneously. In some embodiments, polynucleotides that provide T cells the ability to regulate cell survival and proliferation in response to binding to a CAR, are provided.

The invention provides a bidirectional hCMV-CAG4 promoter and recombinant vectors and recombinant virus comprising the bidirectional hCMV-CAG4 promoter operably linked to a first transgene in one direction and to a second transgene in the opposite direction. The invention also provides methods of making and using such recombinant vectors and recombinant virus.

Methods and compositions for delivering a payload at TnMUC1 positive cancer cells. Anti-TnMUC1 CARs and transgene payloads can be engineered into immune cells so that the transgene payload is expressed and delivered at desired times from the immune cell. Such anti-TnMUC1 CAR T-cells with transgene payloads can be combined with the administration of other molecules, e.g., other therapeutics such as anticancer therapies.

The present invention relates to a nucleic acid expression cassette, in particular for the expression of a human liver-specific and/or liver-expressed protein and/or preferably physiologically active domains and/or fragments thereof in a patient suffering from a monogenetic disorder caused by a mutation in the gene coding for the liver-specific and/or liver-expressed protein.

The present invention is related to a dual promoter lentiviral vector and methods of use for the treatment of diseases and disorders, specifically lysosomal storage disorders.

Provided herein are compositions and methods for high throughout cloning of fused bipartite immunoreceptor polynucleotides encoding cognate pairs of bipartite immunoreceptors. Also provided herein are various applications of the fused bipartite immunoreceptor polynucleotides, expression vectors containing the fused bipartite immunoreceptor polynucleotides, or cells containing the fused bipartite immunoreceptor polynucleotides or expression vectors.

The present invention relates to methods of increasing proliferation and/or programming differentiation status of T cells comprising genetically modifying the cells to inducibly express FOXO1-3A or TCF7 when activated. Also provided are engineered cells modified to inducibly express FOXO1-3A or TCF7 when activated; and methods of treating disease using the engineered cells. Also provided are methods of screening and identifying receptors that specifically bind an antigen or antigens that specifically bind a receptor.

IPEX (Immune dysregulation Polyendocinopathy X linked) syndrome is a primary immunodeficience caused by mutations in the gene encoding the transcription factor forkhead box P3 (FOXP3), which leads to the loss of function of thymus-derived CD4+CD25+ regulatory T (tTreg) cells. Preclinical and clinical studies suggest that T cell gene therapy approaches designed to selectively restore the repertoire of Treg cells by transfer of wild type FOXP3 gene is a promising potential cure for IPEX. However, there is still a need for a vector that can be used efficiently for the preparation of said Treg cells. The inventors thus compared 6 different lentiviral constructs according to 4 criteria (vector titers, level of transduction of human CD4+ T cells, level of expression of FOXP3 and ΔLNGFR genes, degree of correlation between both expression) and selected one construct comprising a bidirectional EFS-PGK promoter that showed remarkable efficiency.

Provided herein are compositions and methods for high throughout cloning of fused bipartite immunoreceptor polynucleotides encoding cognate pairs of bipartite immunoreceptors. Also provided herein are various applications of the fused bipartite immunoreceptor polynucleotides, expression vectors containing the fused bipartite immunoreceptor polynucleotides, or cells containing the fused bipartite immunoreceptor polynucleotides or expression vectors.