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.

Methods of inducing a polarization of macrophages. The method includes obtaining a blood fraction, fractionating the blood fraction to produce a blood fraction, and contacting the blood fraction with a source of macrophages. A blood fraction including platelet-poor plasma polarizes the source of macrophages into M1 macrophages. A blood faction including a protein solution polarizes the source of macrophages into M2 macrophages.

Methods of inducing a polarization of macrophages. The method includes obtaining a blood fraction, fractionating the blood fraction to produce a blood fraction, and contacting the blood fraction with a source of macrophages. A blood fraction including platelet-poor plasma polarizes the source of macrophages into M1 macrophages. A blood faction including a protein solution polarizes the source of macrophages into M2 macrophages.

The present invention relates to methods for producing immuno-stimulatory autologous dendritic cells. The present invention further relates to the use of such cells for treating patients suffering from hyper-proliferative disease such as cancer.

The present invention relates to methods for producing immuno-stimulatory autologous dendritic cells. The present invention further relates to the use of such cells for treating patients suffering from hyper-proliferative disease such as cancer.

Provided herein are cells expressing a first and a second chimeric protein in the cell membrane. Such cells can solve expression problems of CAR constructs caused by these CAR construct's ability to recognize unwanted internal epitopes or exhibiting unwanted signalling due to misfolding/scFv aggregation. The first chimeric protein comprises an extracellular antigen binding unit and an intracellular dimerization domain. The second chimeric protein comprises a lipid anchoring domain, an intracellular dimerization domain and a signaling domain. Accordingly, the expression of the two proteins allows them to translocate to the cell membrane without much interference and subsequently gain signaling capacity when colocalized at the cell membrane.

Provided herein are cells expressing a first and a second chimeric protein in the cell membrane. Such cells can solve expression problems of CAR constructs caused by these CAR construct's ability to recognize unwanted internal epitopes or exhibiting unwanted signalling due to misfolding/scFv aggregation. The first chimeric protein comprises an extracellular antigen binding unit and an intracellular dimerization domain. The second chimeric protein comprises a lipid anchoring domain, an intracellular dimerization domain and a signaling domain. Accordingly, the expression of the two proteins allows them to translocate to the cell membrane without much interference and subsequently gain signaling capacity when colocalized at the cell membrane.

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 an intracellular signaling domain comprising the CD40 cytotail. 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 an intracellular signaling domain comprising the CD40 cytotail. Therapeutic uses of the modified myeloid cell are disclosed.

The present invention relate to autologous isolated unpolarized human macrophages for use in the treatment of liver disease and macrophages for use in a method of treating fibrosis in a human in need thereof.