The present application provides for polypeptides comprising an IL-12 polypeptide, and/or a IL-15 polypeptide, and/or a IL-15 receptor polypeptide, compositions comprising the same, and methods of using the same.

Alveolar-like macrophages and a method for generating alveolar-like macrophages from hemangioblasts is provided. The method comprises the steps of: i) culturing the hemangioblasts in a hematopoietic-inducing medium comprising vascular endothelial growth factor (VEGF), stem cell factor (SCF) and interleukin-3 (IL-3) for a sufficient period of time to generate macrophages, and ii) culturing the macrophages in an alveolar macrophage-inducing medium comprising granulocyte macrophage colony stimulating factor (GM-CSF), and optionally macrophage colony stimulating factor (M-CSF), under suitable conditions and for a sufficient period of time to yield alveolar-like macrophages.

A T cell product for administration to a subject and a use thereof are provided. The product includes at least one allogeneic T cell, which expresses at least one MHC molecule identified as an exogenous source by at least one T cell of the subject. The T cell product can widen the range of a donor and activate an immune response of the subject. The T cell product is used in the preparation of a drug for treating tumors.

The preset disclosure provides methods of promoting a persistent effector function of immune cells, comprising modifying the cells to express reduced levels of NR4A3 gene and/or NR4A3 protein. Also provided are modified cells, e.g., immune cell, which have been modified to express reduced levels of NR4A3 gene and/or NR4A3 protein. Reducing levels of NR4A3 gene and/or NR4A3 protein leads to exhaustion/dysfunction resistant cells, which are apoptosis resistant and also immune checkpoint resistant, and also to the maintenance of anti-tumor function in tumor microenvironments.

Disclosed herein are engineered immune cells that specifically recognizes mesothelin and expresses IL-15 and optionally CCL19. Also disclosed herein are isolated nucleic acid molecules comprising a polynucleotide encoding a chimeric antigen receptor (CAR) comprising an antibody that specifically recognizes mesothelin, and a 4-IBB intracellular region; and a polynucleotide encoding IL-15; and optionally a polynucleotide encoding CCL19, vectors, pharmaceutical compositions comprising the nucleic acid molecules, and methods of using the engineered immune cells.

The present invention provides improved and/or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy for the treatment of non-small cell lung carcinoma (NSCLC), wherein the NSCLC is refractory to treatment with an anti-PD-1 antibody and/or anti-PD-L1 antibody and/or VEGF inhibitor, or wherein the NSCLC has a predetermined tumor proportion score (TPS).

The application provides modified immune effector cells wherein the DNA (cytosine-5)-methyltransferase 3A (DNMT3A)-mediated de novo DNA methylation of the cell genome is inhibited, and IL10 signaling pathway is enhanced. The application also provides related pharmaceutical compositions and the methods for generating such modified immune effector cells. The application further provides uses of such modified immune effector cells for treating diseases such as cancers, infectious diseases and autoimmune diseases.

Provided in the present application is a chimeric antigen receptor, including a GPC3 antigen binding domain, an ICDI, ICD2 or ICD3 intracellular signal stimulation domain with amino acid sequences of SEQ ID NOs: 29, 31 and 33, respectively, and an IL-15-IL-15 fusion protein with an amino acid sequence of SEQ ID NO: 7. After the chimeric antigen receptor is transferred into immune cells, especially iNKT cells, the cell proliferation rate, survival time and tumor killing effect can be effectively improved. Further provided in the present application are a corresponding expression vector, a transduction system, a pharmaceutical use, independent ICDI, ICD2 and ICD3 intracellular signal stimulation domains, and an IL-15-IL-15 fusion protein.

The present invention provides cellular tags including an extracellular region, a transmembrane region, and an optional intracellular region. The extracellular region comprises an IL5 receptor alpha (IL5Ra) sequence linked to a transmembrane domain, and the recombinant polypeptide cannot function in signal transduction. The cellular tags can be operably linked to transgenes. The expression of the cellular tag allows identification, detection, selection, and ablation of cells expressing the transgene and the cellular tag. In some embodiments the genetically modified host cell comprises a transgene comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, and a polynucleotide coding for a cellular tag. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.