Engineered orthogonal cytokine receptor/ligand pairs, and methods of use thereof, are provided.

Provided herein are acute myeloid leukemia antigen targets for chimeric receptors and methods of using same.

The present disclosure relates to the preparation and use of CAR-NK cells which are modified by a nucleic acid targeting compound.

In one embodiment, the present disclosure provides an engineered cell having a first chimeric antigen receptor polypeptide including a first antigen recognition domain, a first signal peptide, a first hinge region, a first transmembrane domain, a first co-stimulatory domain, and a first signaling domain; and a second chimeric antigen receptor polypeptide including a second antigen recognition domain, a second signal peptide, a second hinge region, a second transmembrane domain, a second co-stimulatory domain, and a second signaling domain; wherein the first antigen recognition domain is different than the second antigen recognition domain.

The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease.

Compositions disclosed herein, and methods of use thereof included those for treating or preventing sepsis in a subject in need, including methods of extending of the survival of a subject suffering from sepsis, and reduction of organ dysfunction or failure due to sepsis. Methods of treating or preventing sepsis in a subject in need includes administering compositions comprising early apoptotic cells or early apoptotic cell supernatants. Compositions and methods of use thereof may reduce the negative proinflammatory effect accompanying sepsis. In certain instances, compositions may include additional agents.

Chimeric antigen receptors (CARs) are provided that comprise a CD123-specific antigen recognition domain and IL7Ra transmembrane and intracellular signaling domains (CD123/IL7Ra CARs). In particular embodiments, provided herein are engineered lymphocytes that express and display CD123/IL7Ra CARs, and methods of targeting CD123-positive leukemic cells and treating leukemias, such as acute myeloid leukemia (AML), therewith.

The present disclosure describes compositions and methods for treating cancers such as acute myeloid leukemia (AML), in particular relapsed and refractory AML. The method entails administering to the patient an antibody or a chimeric antigen receptor (CAR)-expressing immune cell targeting a molecule such as CD33, CD123, CD117 or CLL-1 following, or concurrently with, transplanting to the patient an engineered stem cell expressing the same molecule but with a mutation disrupting the epitope to the antibody or CAR. Due to the mutation, the engineered stem cell, unlike endogenous hematopoietic cells, is not targeted by the therapy and thus can supply the patient with functional hematopoietic cells and antigens.

Provided are NK-92 cells expressing a chimeric antigen receptor (CAR). The CAR can comprise an intracellular domain of Fc?RI?. Also described are methods for treating a patient having or suspected of having a disease that is treatable with NK-92 cells, such as cancer or a viral infection, comprising administering to the patient NK-92-CAR cells.

Chimeric antigen receptors containing CD123 antigen binding domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.