A composition for culturing peripheral blood monocyte-derived regulatory T cells includes at least one antibody selected from the group consisting of anti-CD2, anti-CD3, anti-CD7, anti-CD8, anti-CD28, anti-CD30L, anti-CD40, anti-CD70, anti-CD80, anti-CD83, and anti-CD86; at least one cytokine selected from the group consisting of interleukin-2, interleukin-4, interleukin-7, interleukin-12, interleukin-15, interleukin-34, and TGF-β; and superoxide dismutase. A regulatory T cell culturing method using this composition is also provided. The regulatory T cells according obtained by this method can be utilized for treatment of autoimmune diseases.

Disclosed herein is a chimeric antigen receptor T cell therapy for treating patients having a cancer, such as a cancer having one or more solid tumors.

The present invention relates to, inter alia, an engineered cell (e.g., iPSC, IPS-derived NK, or NK cell) comprising a disrupted B2M gene and an inserted polynucleotide encoding one or more of SERPINB9, a fusion of IL15 and IL15Rα, and/or HLA-E. The engineered cell can further comprise a disrupted CIITA gene and an inserted polynucleotide encoding a CAR, wherein the CAR can be an anti-BCMA CAR or an anti-CD30 CAR. The engineered cell may further comprise a disrupted ADAM17 gene, a disrupted FAS gene, a disrupted CISH gene, and/or a disrupted REGNASE-1 gene. Methods for producing the engineered cells are also provided, and therapeutic uses of the engineered cells are also described. Guide RNA sequences targeting described target sequences are also described.

ILC2 cells play a role in the pathogenesis of graft versus host disease (GvHD) and idiopathic pneumonia syndrome (IPS), both conditions associated with allogeneic stem cell transplantation. Infusion of IL-33 activated ILC2 cells into patients with ongoing GvHD or IPS, or prior to onset of GvHD or IPS in susceptible patients, substantially ameliorates the disease and improves survival.

The invention provides culture platforms, cell media, and methods of differentiating pluriptent cells into hematopoietic cells. The invention further provides pluripotent stem cell-derived hematopoietic cells generated using the culture platforms and methods disclosed herein, which enable feed-free, monolayer culturing and in the absence of EB formation. Specifically, pluripotent stem cell-derived hematopoietic cell of this invention include, and not limited to, iHSC, definitive hemogenic endothelium, hematopoietic multipotent progenitors, T cell progenitors, NK cell progenitors, T cells, and NK cells.

Disclosed are means, methods, and compositions of matter useful for treatment of autoimmunity comprising exposing patient T cells fibroblasts possessing tolerogenic properties. In one embodiment peripheral blood mononuclear cells are cultured in the presence of CD73 selected fibroblasts alone or in the presence of interleukin-2, and/or IL-7, and/or TGF-beta, and/or PGE-2 for a period of time sufficient to endow tolerogenic properties. Said tolerogenic properties include ability to suppress adaptive or innate immune responses. In another embodiment the disclosure provides methods of generating antigen specific immune regulatory cells by culture of T cells together with fibroblasts in the presence of antigen to which specific immune regulation is desired.

The present disclosure relates to an engineered immune cell and use thereof. The present disclosure provides an engineered immune cell comprising a CAR or engineered TCR, which CAR or engineered TCR can comprise a first antigen binding domain and a second antigen binding domain. The engineered immune cells of the present disclosure, when administered into a subject, can inhibit the host immune cells such as T cells and/or NK cells and enhance the survival and persistence of the engineered immune cells in vivo, thereby exhibiting more effective tumor killing activity.

This disclosure provides methods for producing multi-TCR T cells with enhanced anti-tumor phenotypes. The T cells are made from hematopoietic stem cells by introducing into the hematopoietic stem cells a first TCR and subsequently a second TCR.

Cartridges for manufacturing a population of cells suitable for formulation as a cellular therapeutic are disclosed herein, along with systems and instruments for operating the cartridges and performing methods to generate the population of cells suitable for formulation as a cellular therapeutic. The population of cells suitable for formulation as a cellular therapeutic can be immunological cells, such as T lymphocytes, including endogenous T cells (ETCs), tumor infiltrating lymphocytes (TILs), CAR T-cells, TCR engineered T-cells, or otherwise engineered T-cells. The systems and methods can be largely automated.

Provided is a T cell receptor (TCR) capable of specifically binding to KRAS G12V mutant antigens; the mutant antigen short peptide VVGAVGVGK is capable of forming a complex with HLA A1101, and the TCR specifically binds to said complex. Also provided in the present invention are a nucleic acid molecule encoding the TCR and a vector comprising the nucleic acid molecule. Also provided are TCR-transduced cells.