Provided herein are methods for preparing and characterizing SARS-co2 antigen specific immune cell cultures and preparations and methods of using the same in adoptive immunotherapy for cancer, infections and immune disorders. Also, provided are compositions and methods for generating immune cells expressing synthetic antigen binding receptors targeting SARS-cov2 and methods of use of these cells for the treatment and prevention of COVID-19. Also provided are compositions and methods for determining immune response to SARs-cov2 in a subject, detecting SARS-cov2, measuring cytotoxicity induced by SARS-cov2, and detecting the expression and cytotoxicity of synthetic antigen binding receptors targeting SARS-cov2.

Provided herein are humanized mouse models and methods for determining whether administration of engineered immune cell therapies likely elicit cytokine release syndrome and/or determining the efficacy of an anti-disease therapy. Further, the models provided herein may be used to test the efficacy of different anti-CRS therapies.

Provided herein are humanized mouse models and methods for determining whether administration of engineered immune cell therapies likely elicit cytokine release syndrome and/or determining the efficacy of an anti-disease therapy. Further, the models provided herein may be used to test the efficacy of different anti-CRS therapies.

Described herein are improved media for culturing immune cells, and methods of use thereof. In particular, cell growth media described herein are particularly suitable for T-cell expansion, which can be used for manufacture of cells useful in adoptive cell therapies, including therapies using chimeric antigen receptors (e.g., CAR-T cell therapy).

Methods, compositions and kits for producing functional antigen-specific regulatory T cells (Tr1 cells) by reprogramming non-Tr1 target cells with suitable transcription factors.

A population of genetically engineered T cells, comprising a disrupted Reg1 gene and/or a disrupted TGFBRII gene. Such genetically engineered T cells may comprise further genetic modifications, for example, a disrupted CD70 gene. The population of genetically engineered T cells exhibit one or more of (a) improved cell growth activity; (b) enhanced persistence; and (c) reduced T cell exhaustion, (d) enhanced cytotoxicity activity, (e) resistant to inhibitory effects induced by TGF-b, and (f) resistant to inhibitory effects by fibroblasts and/or inhibitory factors secreted thereby, as compared to non-engineered T cell counterparts.

The present disclosure features allogeneic modified cells (e.g., T- or NK-cells) having increased persistence, increased resistance to immune rejection, or decreased risk of eliciting a host-versus-graft reaction, or a combination thereof. Methods for producing and using the same are also provided.

The present disclosure features allogeneic modified cells (e.g., T- or NK-cells) having increased persistence, increased resistance to immune rejection, or decreased risk of eliciting a host-versus-graft reaction, or a combination thereof. Methods for producing and using the same are also provided.

Compositions and methods for eradicating tumor cells using novel compositions are contemplated. In one aspect, a pharmaceutical composition comprising a CAR scaffold and an antigen binding domain in a single chimeric species is provided. In some aspects, the CAR scaffold may comprise a CD28 costimulatory signaling region and a CD3 (activation domain or a complete CD3 activation domain. In some aspects, the CAR scaffold may be codon-optimized for improved expression in mammalian cell lines and/or for improved function upon transfection into natural killer (NK) or other immune cells. In further aspects, the antigen binding domain may comprise a VL and VH domain linked by a spacer and may be codon optimized. A CD64 leader sequence may be attached to the antigen binding domain, e.g., at the N-terminus of the antigen binding domain.

The present disclosure provides compositions and methods for producing modified cells (e.g., synthetic tumor-infiltrating lymphocytes or TILs). The modified cells can be used to prepare a pharmaceutical composition to be administered into a subject in need thereof. The modified cells can be polyclonal TCR-T cells expressing two or more different subject-specific T-cell receptors (TCRs).