Compositions and combination cellular therapies with natural killer (NK) cells and macrophages for treating disease such a leukemia are disclosed herein. The compositions and therapeutic methods of administration may optionally include antibodies, such as anti-CD47 or other SIRP signaling inhibitors. The NK and macrophage cells may be produced from stem cells, and may optionally be produced from induced pluripotent stem cells (iPSCs), where the NK and macrophage cells may have enhanced antibody-dependent cellular cytotoxicity (ADCC). These immune cells may also be incorporated into pharmaceutical compositions. Methods for making the immune cells and pharmaceutical compositions, and methods of use thereof, are also provided.

Compositions and methods are provided for treating lymphoma in an individual by targeting engineered phagocytes to lymphoma cells. In particular, the phagocytes provided for administration to an individual, who has lymphoma, are engineered to express a chimeric antigen receptor (CAR) that specifically binds to an antigen present on lymphoma cells. The CAR localizes the engineered phagocytes to sites where lymphoma cells are present. In some embodiments, phagocytic activity of the phagocytes is enhanced by further engineering the phagocytes to express a hyperactive Rac GTPase.

The present disclosure provides new anti-cancer immune cells engineered to express chimeric receptors which, unlike the conventional chimeric antigen receptors (CAR), employ the extracellular domain of PD-1 that is capable of binding PD-L1 that is expressed on a target tumor cell. The immune cell is preferably an immature myeloid cell that is p50 deficient. Such an engineered immune cell exhibits improved therapeutic efficacy as compared to the conventional immune cell therapies and is more broadly applicable to different types of cancers expressing, or induced to express PD-L1.

Described herein are compositions comprising subsets of monocyte having distinct functional properties and methods for using the same to treat infectious disease.

The present disclosure provides methods for preparing immune cells that express a chimeric receptor. The immune cells, preferably p50 deficient immature myeloid cells, exhibited improved therapeutic efficacy as compared to the conventional immune cell therapies and are more broadly applicable to different types of cancers. The preparation methods preferably include inactivating p50 in a progenitor cell, expanding the cell under hypoxic conditions, transducing a polynucleotide that encodes the chimeric receptor, and differentiating the engineered progenitor cell to an immature myeloid cell.

Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and/or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella, or by modification of the genes so that functional flagella are not produced, and/or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellin.sup. and/or pagP.sup.. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine or purine auxotrophs. The bacteria optionally are one or more of asd.sup., purI.sup., and msbB.sup.. The immunostimulatory bacteria, such as Salmonella species, are modified to encode immunostimulatory proteins that confer anti-tumor activity in the tumor microenvironment, and/or are modified so that the bacteria preferentially infect immune cells in the tumor microenvironment, or tumor-resident immune cells, and/or are modified to induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the immunostimulatory bacteria.

The present disclosure provides compositions and methods comprising chimeric antigen receptors (CARs) specific for amyloid beta (A) and/or Tau. In certain embodiments, the CARs do not comprise an intracellular domain. Methods of treatment are also disclosed herein.

A conditioned cell culture medium of CD11b.sup.low human macrophages or a biologically active fraction thereof can be prepared by a method that includes (i) culturing a population of human mononuclear cells of the monocyte/macrophage lineage for 5-7 days, so as to induce differentiation of the mononuclear cells to macrophages; (ii) incubating the macrophages obtained in (i) with apoptotic cells or in the presence of a pro-resolving lipid mediator to reduce the CD11b expression, thus obtaining a culture of CD11b.sup.low macrophages; and (iii) collecting the conditioned cell culture medium of CD11b.sup.low macrophages. Pharmaceutical compositions containing the CD11b.sup.low macrophages conditioned medium or a culture of CD11b.sup.low macrophages can be used in the treatment of cancer or fibrosis.

Provided herein are compositions comprising aptamers that specifically bind monocytes and/or macrophage and methods for their use. These aptamer compositions can be used in methods for isolating and/or enriching monocytes and/or macrophages or depleting cell populations of monocytes and/or macrophages. Further provided are methods of using the aptamers or cell populations generated using them in the methods disclosed herein for therapies and/or drug delivery.

Modified macrophage immune cells are provided for treatment of cancer and other diseases.