A method for producing genetically engineered immune cells, e.g. T cells, or iPSCs which uses an RNA-scaffold mediated base editing system. The method enables precise modifications to be made to the genome whilst minimizing the possibility of off-target effects, making the method particularly suitable for therapeutic applications.

In alternative embodiments, provided are compositions, including recombinant expression systems and vectors, products of manufacture and kits, and methods, for remotely-controlled and non-invasive manipulation of intracellular nucleic acid expression, genetic processes, function and activity in live cells such as T cells in vivo, for example, activating, adding functions or changing or adding specificities for immune cells, for monitoring physiologic processes, for the correction of pathological processes and for the control of therapeutic outcomes. In alternative embodiments, provided are blue-light-mediated light-inducible nuclear translocation and dimerization (LINTAD) systems for gene regulation to control cell activation based on the integration of light-sensitive LOV2-based nuclear localization, light-induced active transportation via the biLINuS motif, and CRY2-CIB1 dimerization that feature high spatiotemporal control to control or alter cell activities in vivo, for example, to limit CAR T cell activity to the tumor site for immunotherapy applications.

Disclosed are compositions and methods for targeted treatment of SSTR-expressing cancers. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer to target and kill SSTR-expressing cancers. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of providing an anti-tumor immunity in a subject with a SSTR-expressing cancer, such as a neuroendocrine tumor, that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

A modified immune cell that has attenuated expression and/or activity of YTH N6-Methyladenosine RNA Binding Protein 2 (YTHDF2), and enhanced anti-tumor activity. A composition for stimulating T cell-mediated immune response to a cancer cell and/or a tumor antigen, including an agent capable of attenuating the expression and/or activity of YTHDF2, and a pharmaceutically acceptable excipient. A composition for treating cancer, comprising an agent capable of attenuating the expression and/or activity of YTHDF2. A method for activating an immune cell. A method for generating an immune cell. A method for treating a disease, disorder or condition associated with an expression of a tumor antigen in a subject in need thereof. A method for stimulating a T cell-mediated immune response to a cancer cell and/or a tumor antigen in a subject in need thereof.

The present disclosure relates to methods for enhancing the efficiency of therapies involving immune effector cells such as T cells engineered to express antigen receptors such as T cell receptors (TCRs) or chimeric antigen receptors (CARs). It is demonstrated herein that such antigen receptor-engineered immune effector cells, even when provided to a subject in sub-therapeutic amounts, are extremely effective in the treatment of cancer diseases, even those cancer diseases that are known to be difficult to treat with antigen receptor-engineered immune effector cells, such as solid tumors or cancers, if additionally target antigen for the antigen receptor is provided to the subject. Immune effector cells may be engineered ex vivo or in vitro and subsequently the immune effector cells may be administered to a subject in need of treatment, or immune effector cells may be engineered in vivo in a subject in need of treatment.

The present invention relates to a human induced pluripotent stem cell line transformed with fluorescent protein-tagged CYP1A1 and an AHR modulator screening method using the same. Specifically, a human-induced pluripotent stem cell line (hiPSC line) in which a gene was edited to express a cytochrome P450 1A1 (CYP1A1) protein in a state of fusion with a fluorescent protein without inhibiting its unique function was prepared, and it was confirmed that an AHR modulator could be screened by screening cells in a living state using the cell line-derived liver cells better than in the case of using existing human primary hepatocytes (hPH) or HepG2 cells. Therefore, the CYP1A1-mCherry hiPSC cell line of the present invention can be effectively used for screening AHR modulating compounds.

The present disclosure pertains to methods of modifying an immune cell by delivering a modified messenger RNA (mRNA) encoding a chimeric antigen receptor (CAR) and modified immune cells comprising CARs.

Disclosed are engineered multicellular organisms. Also disclosed are systems and methods for designing, preparing, and utilizing the engineered multicellular organisms.

The present disclosure provides compositions and methods for cell transplantation therapy based on forced expression of an exogenous HLA-F protein in donor cells to be transplanted into a subject. In some embodiments, the donor cells express an exogenous chimeric HLA-F protein comprising an extracellular region comprising an HLA-F alpha 1 domain, an HLA alpha 2 domain, an HLA-F alpha 3 domain, a linker and a β2m protein.

The present disclosure relates to antigen presenting cells and uses thereof for treating sepsis. In some aspects, disclosed herein is an antigen presenting cell, comprising: a lipid-based nanoparticle, comprising: a recombinant polynucleotide, comprising: a first nucleic acid encoding an antimicrobial peptide; a second nucleic acid encoding cathepsin B; and a third nucleic acid encoding a linker; and a vitamin-lipid.