The present disclosure relates to the genetically modified non-human animals that express a human or chimeric TIGIT (e.g., humanized TIGIT), and methods of use thereof.

A primatized rodent or swine, and methods of making and using the primatized rodent or swine, are provided.

A non-human mammalian model for human diseases or disorders comprising a non-human neutrophil depleted mammalian host engrafted with a human skin equivalent (huSE) and human immune cells.

Circular RNA and transfer vehicles, along with related compositions and methods are described herein. In some embodiments, the inventive circular RNA comprises group I intron fragments, spacers, an IRES, duplex forming regions, and an expression sequence. In some embodiments, the expression sequence encodes a chimeric antigen receptor (CAR). In some embodiments, circular RNA of the invention has improved expression, functional stability, immunogenicity, ease of manufacturing, and/or half-life when compared to linear RNA. In some embodiments, inventive methods and constructs result in improved circularization efficiency, splicing efficiency, and/or purity when compared to existing RNA circularization approaches.

Provided are non-human animals, including humanized bone marrow/liver/thymus (BLT) non-human animals, that include a recipient immunodeficient animal with human thymus tissue and human liver tissue, both implanted under a kidney capsule of the recipient immunodeficient animal, and transplanted hematopoietic stem cells derived from a human liver tissue. Such non-human animals have human thymus tissue and human liver tissue that are autologous with the hematopoietic stem cells derived from the human liver tissue. Methods of making such BLT non-human animals are also provided. Also disclosed herein are human immune system non-human animals and methods of making the same.

A tetravalent, homodimer-type bispecific antibody molecule that simultaneously targets immune effector cell antigen CD3 and human epidermal growth factor receptor 2 (Her2); the bispecific antibody molecule comprises, from in sequence from N-terminus to C-terminus, a first single-chain Fv capable of specifically binding to Her2, a second single-chain Fv capable of specifically binding to CD3, and an Fc fragment; the first and second single-chain Fv are connected by means of a connection peptide, and the second single-chain Fv is connected to the Fc directly fragment or is connected by means of a connection peptide; the Fc fragment does not have effector functions such as CDC, ADCC and ADCP. The bispecific antibody may significantly inhibit or kill tumor cells, and has controlled toxic side effects that may be caused by excessive activation of effector cells. The maximum safe starting dose in preclinical toxicology evaluation tests is significantly higher than other doses having the same target, and no systemic immunotoxicity occurs, suggesting that the drug administration safety window for the bispecific antibody is wide; in addition, said bispecific antibody is a homodimer that does not experience the problem of heavy chain and light chain mismatching; the steps of purification are simple and efficient, expression is high, and the physicochemical and in vivo stability of the antibody are significantly improved.

Disclosed herein are chimeric blastocysts, such as chimeric blastocysts derived from a host blastocyst from a first mammalian species and having donor pluripotent stem cells from a second mammalian species, wherein the donor pluripotent stem cells have reduced expression or reduced biological activity of one or more proteins in the TLR/NF-kB signaling pathway or the p53 pathway. Methods of preparing chimeric blastocysts and methods of obtaining mammalian organs and tissues are also provided.

Cytotoxic T cells derived from human T cell-derived iPS cells may avoid an NK cell missing-self response and may be used for allogeneic administration while maintaining a strong antitumor effect of antigen-specific CTLs. A method may produce a cytotoxic T cell derived from a human T cell-derived iPS cell expressing HLA class I of HLA-restricted class I of an antigen epitope of a CTL and HLA-E. Such a method may include: knocking out all HLA class I of the human T cell-derived iPS cell; introducing a gene of the HLA-restricted HLA class I of the antigen epitope of the CTL and a gene of the HLA-E into the T-iPS cell in which all HLA class I have been knocked out; and redifferentiating the genetically introduced T-iPS cell into a CD8 single-positive T cell.

The present disclosure provides a method of generating a T cell comprising a transgene integrated at a first site within the genome of the T cell, wherein the transgene encodes a polypeptide that is a subunit of a negative elongation factor (NELF) complex. The T cells can be administered to treat cancer and infectious disease.

The invention relates to a new, spontaneous mouse lymphoma cell line displaying CD19, B220, MHC II, surface IgG2a/kappa chain and MAC-1, which is negative for CD5, animal models of B-cell lymphoma based on said cell line and methods for assessing lymphoma propagation and lymphoma expansion based on said cell line.