The disclosure relates to immune cells comprising one or more vectors comprising a nucleic acid sequence encoding a chimeric antigen receptor specific for CD19 and a nucleic acid sequence encoding an enhancer of T cell priming (e.g., IL-18), compositions comprising the T cells, and methods of generating and/or using the T cells to treat diseases associated with the expression of CD19.

Described herein are chimeric receptors comprising G-CSFR extracellular domains and the intracellular domains of various multi-subunit cytokine receptors for selective activation of cytokine signaling in cells of interest. In certain aspects, the selective activation of cytokine signaling in cells expressing the chimeric receptors described herein includes the ability to specifically stimulate adoptively transferred cells.

The invention provides a natural killer (NK) cell engineered to express a chimeric antigen receptor (CAR), wherein the CAR comprises the extracellular domain of CD27 or a CD70-binding portion thereof, as well as compositions comprising the engineered NK cell, methods for producing the engineered NK cell, and therapeutic applications of the engineered NK cell, such as for treating neoplastic diseases.

The technology described herein is directed to Natural Killer (NK) cell CAR polypeptides comprising intracellular signaling domains, intracellular costimulatory domains, and/or transmembrane domains from NK-associated polypeptides. In various aspects, described herein are polynucleotides, vectors, or cells expressing said NK CAR polypeptides, and pharmaceutical compositions comprising said NK CAR polypeptides, polynucleotides, vectors, or cells. Also described herein are methods of using said NK CAR polypeptides, for example to treat various diseases and disorders, such as cancer or infectious diseases.

The present invention relates to a proliferation enhancer. The enhancer comprises a protein molecule capable of initiating the cellular STATS and/or STAT3 signaling pathway and comprising the intracellular domain, the transmembrane domain and the extracellular domain. The present invention further relates to a lymphocyte expressing the proliferation enhancer and the use thereof as an immunotherapy drug.

Described herein are methods for producing and utilizing an alternative signal 1 domain to construct an optimally signaling CAR. Alternative signal 1 domains of the present technology are based on alternatives to CD3, including mutated ITAMs from CD3 (which contains 3 IT AM motifs), truncations of CD3, and alternative splice variants known as CD3s, CD3 theta, and artificial constructs engineered to express fusions between CD3s or CD30 and CD3. CAR polypeptides comprising alternative signal 1 domains are utilized to engineer CAR T cells. Further, this technology related to methods of treating cancer by administering to a subject in need thereof CAR T cells comprising alternative signal 1 domains.

Compositions and methods for therapeutic use of engineered myeloid cells are described. Methods for increasing therapeutic effectiveness of immune cells by use of an immune cell inhibitory agent prior to therapy is described. Effective use of myeloid cells in combination therapy is described.

Chimeric Antigen Receptors (CARs) comprising a costimulatory sequence which is, or which is derived from, the intracellular domain of CD226, or a fragment thereof, are disclosed. Also disclosed are compositions comprising such CARs, and uses and methods using the same.

Disclosed herein are compositions and methods relating to agents that target a lineage-specific cell-surface antigen and a population of hematopoietic cells that are deficient in the lineage-specific cell-surface antigen for immunotherapy of hematological malignancies.

Provided herein are immune cells and methods of use, wherein the immune cells include a chimeric antigen receptor (CAR), wherein the CAR comprises an extracellular antigen binding domain that binds specifically to a first epitope; and an inhibitory chimeric antigen receptor (iCAR), wherein the iCAR comprises an extracellular antigen binding domain that binds specifically to a second epitope, wherein the immune cell is activated when the immune cells binds to the first epitope and does not bind to the second epitope; and wherein the immune cell is inactivated when the immune cell binds to the first and second epitopes.