Described herein are compositions and methods for treating various indications in a subject including, but not limited to, atherosclerosis, cardiovascular diseases, inflammation, chronic inflammatory diseases, wounds, and spinal cord injuries. In some embodiments, the compositions and methods comprise a modified macrophage or monocyte comprising surface-expressed CD47-targeted chimeric antigen receptor (CAR) proteins and lipid-based particles conjugated to a surface of the modified macrophage or monocyte, wherein the lipid-based particles comprise a -cyclodextrin (-CD). In some embodiments, the lipid-based particles comprise lipid nanoparticles (LNPs).

Provided is a method of treating cancer in an individual by administering to the individual modified cells that express a chimeric antigen receptor (CAR) that contain a TIGIT extracellular domain that can bind to poliovirus receptor (PVR), a CD28 segment, and a CD3 segment. The modified cells may co-express and secrete a Bi-specific T cell engager (BiTE). The BiTE includes a segment that can specifically bind to human Folate Receptor alpha (FR) and a segment that that can specifically bind to a human CD3 segment. Modified cells that express the CAR, and may also express and secrete the BiTE, and polynucleotides encoding the CAR and the BiTE, are also provided.

Provided is a pharmaceutical composition or combination comprising: (i) an isolated population of cells comprising V17+CD8+ T cells, (ii) one or more T cell engagers; and (iii) a pharmaceutically acceptable excipient. Also provided are methods of using the isolated population of cells comprising V17+CD8+ T cells and the T cell engagers for redirecting a T cell to a target cell, inhibiting the growth or proliferation of a target cell, eliminating a target cell, or treating a disease or disorder.

The present invention relates to: a chimeric antigen receptor comprising an antigen-binding site specifically binding to HLA-G, which is an immune checkpoint; immune cells into which the receptor is introduced; and use thereof. The immune cells can effectively remove cancer cells in which an immune checkpoint is expressed, such that even the activation of endogenous immune cells, which had been suppressed by immune checkpoints, can be expected, and thus can be effectively used as an immunotherapeutic method for various cancer diseases related to HLA-G.

Provided is a T cell for securing the purity and number of cells sufficient for treatment. Also provided is a method of generating the T cell. More specifically, provided are homogeneous T cells excellent in that the T cells are not affected by exhaustion of the cells. The foregoing is achieved by T cells obtained by subjecting induced pluripotent stem cells (iPS cells) to differentiation induction treatment. Specifically, the foregoing is achieved by T cells generated by subjecting iPS cells having a rearranged TCR gene ( TCR-type iPS cells) to differentiation induction treatment. According to the method of generating the T cell of the present invention, there can be provided T cells and a cell population of T cells that have an excellent function of having antigen-specific cytotoxic activity in an MHC-unrestricted manner, and that are more homogeneous and have a higher effect than T cells separated from peripheral blood.

The present disclosure provides the use of fratricide-resistant chimeric antigen receptor T (CAR-T) cells targeting antigens expressed by T cell malignancies.

The present disclosure provides reagents and methods for treating disease using modified immune cells (e.g., T cell comprising CAR or TCR) in combination with an agent associated with induction of immunogenic cell death (ICD) and optionally further in combination with an agent that specifically binds to and/or inhibits an immune suppression component and/or an agonist of an immune stimulatory molecule.

Immunomodulating polynucleotides are disclosed. The immunomodulating polynucleotides may contain 5-modified uridine, 5-modified cytidine, a total of from 6 to 16 nucleotides, and/or one or more abasic spacers and/or internucleoside phosphotriesters. Also disclosed are conjugates containing a targeting moiety and one or more immunomodulating polynucleotides. The immunomodulating polynucleotides and conjugates may further contain one or more auxiliary moieties. Also disclosed are compositions containing the immunomodulating polynucleotides or the conjugates containing one or more stereochemically enriched internucleoside phosphorothioates. Further disclosed are pharmaceutical compositions containing the immunomodulating polynucleotides or the conjugates and methods of their use.

The invention relates to the field of medicine and genetic engineering, specifically to guide RNAs and DNA fragments and to cell selection methods, which can be used in CRISPR-Cas9 systems for producing lines of natural killer cells with a PD-1 knockout gene and increased production of TRAIL or Fas-ligand proteins. Methods are disclosed for producing modified lines of NK cells: with a PD-1 knockout gene and constitutive Fas-ligand overexpression, with a PD-1 knockout gene and constitutive TRAIL overexpression, and also a method is described for selecting modified NK cells with a PD-1 knockout gene, which is carried out using a zeocin selection marker. The invention makes it possible to produce a high yield of modified lines of NK cells that are highly active in inhibiting the growth of tumour cells.

The disclosure describes T cells that express chimeric antigen receptors (CARs), as well as pharmaceutical compositions comprising T cells and methods of making and using such T cells. Particularly, this disclosure describes T cells expressing a CAR that binds to CD64, and methods of use in treating acute myeloid leukemia.