The present invention provides composition kits and methods for treating cancer in a human by immunotherapy using successive doses of CAR-T cells with no or reduced anamnestic immune reaction in one individual (P).

Methods are provided for treating a subject for an EGFRvIII expressing glioblastoma. The methods of the present disclosure involve administering to the subject a molecular circuit that is primed by EGFRvIII to induce one or more encoded therapeutics specific for one or more antigens expressed by the glioblastoma. Nucleic acids containing sequences encoding all or portions of such circuits are also provided, as well as cells, expression cassettes and vectors that contain such nucleic acids. Also provided are kits for practicing the described methods.

The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

Described herein are immunoresponsive cells which are useful for their preventive and therapeutic potential against autoimmune diseases and rejections of solid organ transplants.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

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.

Disclosed herein are genetically engineered hematopoietic cells, which express one or more Krebs cycle modulating polypeptides, and optionally a chimeric receptor polypeptide (e.g., an antibody-coupled T cell receptor (ACTR) polypeptide or a chimeric antigen receptor (CAR) polypeptide) capable of binding to a target antigen of interest. Also disclosed herein are uses of the engineered hematopoietic cells for inhibiting cells expressing a target antigen in a subject in need thereof.

The present application provides T cells comprising an antigen and an adjuvant, methods of manufacturing such T cells, and methods of using such T cells, such as for modulating an immune response in an individual.

The present invention refers immune cells expressing a TCR and a co-stimulatory receptor which are poly functional, i.e. secreting 2 or more proteins. Exemplary immune cells express a(i) T cell receptor (TCR) specific for the PRAME peptide SLLQHLIGL or a TCR specific for NY-ESO-1 peptide SLLMWITQC and (ii) a chimeric co-stimulatory receptor comprising an extracellular domain derived from PD-1 (CD279) and an intracellular domain derived from 4-1BB (CD137).

A method of treating a cancer, the method comprising: providing a modified macrophage or monocyte that contains an exogenous nucleic acid sequence encoding a Hom-1 polypeptide or a fragment thereof that contains the Hom-1 homeobox domain, wherein the modified macrophage or monocyte expresses the Hom-1 polypeptide or the fragment thereof; and administering the modified macrophage or monocyte to a subject with a cancer.