The present invention provides compositions of recombinant human lysosomal acid lipase having particular glycosylation patterns for internalization into target cells, a vector containing the nucleic acid encoding human lysosomal acid lipase, a host cell transformed with the vector, pharmaceutical compositions comprising the recombinant human lysosomal acid lipase and method of treating conditions associated with lysosomal acid lipase deficiency.

The present invention comprises a method of downregulating intracellular defenses by administering (5Z)-7-Oxozeaenol. This allows for improved delivery of RNA based gene vectors to natural killer, stem and macrophage cells. The resulting cells can be used in adoptive cell transfer therapies. Also provided are methods of treating virally induced inflammation via administration of (5Z)-7-Oxozeaenol together with an anti viral therapeutic.

A cell for producing retroviral vectors comprising nucleic acid sequences encoding: i) gag-pol; ii) env; iii) the RNA genome of the retroviral vector; and iv) optionally rev, or a functional substitute thereof, wherein at least two nucleic acid sequences are located at the same genetic locus; and wherein the at least two nucleic acid sequences are in reverse and/or alternating orientations.

The invention provides improved T cell compositions and methods for manufacturing T cells. More particularly, the invention provides methods of T cell manufacturing that result in adoptive T cell immunotherapies with improved survival, expansion, and persistence in vivo.

The present disclosure provides an automated method of producing genetically modified immune cells, including chimeric antigen receptor T (CAR T) cells, utilizing a fully-enclosed cell engineering system.

The presently disclosed subject matter provides for antigen-recognizing receptors that specifically target CD33 and cells comprising such CD33-targeted antigen-recognizing receptors. The presently disclosed subject matter further provides uses of the CD33-targeted antigen-recognizing receptors for treatment.

The invention is based on antigen binding proteins (ABPs) such as T-cell receptors (TCR) expressed on T-cells, which have a specificity to bind to MIC presented Rac2 and Rac1 derived neo-epitopes. Hence, such MHC presented peptides are derived from mutated versions of Rac1 and Rac2, such as preferably RAC2.sup.P29L and/or RAC1.sup.P29S. Provided are isolated ABPs as well as genetic constructs expressing the ABPs, recombinant host cells harboring the ABP of the invention and methods for producing such ABPs and host cells. Moreover, provided are medical applications involving the TCR of the invention, for example in context of an adoptive T-cell therapy.

Provided herein are chimeric antigen receptor (CAR) viral libraries and methods of making the same. In some embodiments, the CAR comprises an intracellular domain (ICD) with at least one immune activation signaling domain, one co-stimulatory domain, and one or more inhibitory signaling domain or signaling domain from non-T cell lineages. In some embodiments, the signaling domains of the ICD are joined by distinct linkers of 10 amino acids. In some embodiments, the CARs contain a 18-nucleotide barcode in the 3 untranslated region. Also provided herein, are CAR cell libraries and methods of making the same.

The present invention provides methods for producing recombinant viral particles based on the use of exogenous mRNAs to supply various helper factors for assembly of viral particles, purified recombinant viral particles produced using such methods, and methods of using such viral particles.

Provided are a method for establishing a lentiviral vector system capable of directly reflecting type I interferon response, and applications thereof. The method for establishing the lentiviral vector system comprises: cutting a Gaussia luciferase at the position of amino acid 109, removing 16 amino acids from N-terminus, and cloning the two polypeptides into a lentiviral vector to form a lentiviral BiLC expression vector; and cloning a shuttle plasmid of pEntry-IRF3 or pEntry-IRF5 or pEntry-IRF7 by homologous recombination into the lentiviral BiLC expression vector, so as to construct a lentiviral vector IRF3-BiLC or IRF5-BiLC or IRF7-BiLC capable of directly reflecting type I interferon response.