The present application provides compositions and methods for producing antigen presenting cells (APCs) from monocytes (e.g., monocytes from cancer patients) that involve an IL-10 receptor activator (e.g., IL-10), IFN receptor activator (e.g., IFN), TNF receptor activator (e.g., TNF), IL-4 receptor activator (e.g., IL-4), GM-CSF receptor activator (e.g., GM-CSF), and/or IL-6 receptor activator (e.g., IL-6). APCs produced accordingly are also provided, as well as methods of activating immune cells (e.g., T cells) via co-culturing with APCs. The activated immune cell compositions and the methods of treatments that involve the activated immune cells are also provided.

The present invention relates to the use of immunoregulatory macrophages for treating diseases that are associated with pathological changes of the blood vessels. The present invention particularly relates to the use of immunoregulatory macrophages for treating micro- and macroangiopathies of the lower limbs. The invention furthermore relates to the use of immunoregulatory macrophages for promoting tissue remodelling to facilitate wound healing. Pharmaceutical compositions for use in the recited treatments are also disclosed which comprise the immunoregulatory macrophages.

The present invention relates to the use of immunoregulatory macrophages for treating diseases that are associated with pathological changes of the blood vessels. The present invention particularly relates to the use of immunoregulatory macrophages for treating micro- and macroangiopathies of the lower limbs. The invention furthermore relates to the use of immunoregulatory macrophages for promoting tissue remodelling to facilitate wound healing. Pharmaceutical compositions for use in the recited treatments are also disclosed which comprise the immunoregulatory macrophages.

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.

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.

A modified myeloid cell comprises a chimeric antigen receptor (CAR), or a modified induced pluripotent stem cell (iPS) or hematopoietic stem cell (HSC) comprising a CAR, wherein said CAR comprises an extracellular antigen-binding domain which binds to a tumor antigen or a tumor microenvironment (TME) antigen; a transmembrane domain; and a first intracellular signaling domain comprising the CD40 cytotail, which is fused to a second intracellular signaling domain comprising the CD3zeta intracellular domain. Therapeutic uses of the modified myeloid cell are disclosed.

A modified myeloid cell comprises a chimeric antigen receptor (CAR), or a modified induced pluripotent stem cell (iPS) or hematopoietic stem cell (HSC) comprising a CAR, wherein said CAR comprises an extracellular antigen-binding domain which binds to a tumor antigen or a tumor microenvironment (TME) antigen; a transmembrane domain; and a first intracellular signaling domain comprising the CD40 cytotail, which is fused to a second intracellular signaling domain comprising the CD3zeta intracellular domain. Therapeutic uses of the modified myeloid cell are disclosed.

Provided are chimeric antigen receptor (CAR) that bind to beta amyloid, macrophages (CAR-Ms) that express the CAR, and compositions comprising the same. Also provided are methods for reducing one or more symptoms associated with Alzheimer's disease using the CAR-Ms.

Provided are chimeric antigen receptor (CAR) that bind to beta amyloid, macrophages (CAR-Ms) that express the CAR, and compositions comprising the same. Also provided are methods for reducing one or more symptoms associated with Alzheimer's disease using the CAR-Ms.

The present invention relates to novel immunoregulatory macrophage cells which are useful in the treatment of different immunological and non-immunological diseases and conditions. The cells are characterized by a specific marker and activity pattern which distinguishes them from other cells. The novel immunoregulatory macrophage cells have a high phagocytosing capacity and are capable to suppress the proliferation of T cells. The invention also provides a novel process for preparing immunoregulatory macrophage cells in suspension culture from blood monocytes. The process is amenable to a high degree of automation. In a still further aspect, the invention relates to a pharmaceutical composition comprising the immunoregulatory macrophage cells of the invention.