The present disclosure provides a population of polydonor CD4.sup.IL-10 cells generated by genetically modifying CD4.sup.+ T cells from at least two different T cell donors. Further provided are methods of generating the polydonor CD4.sup.IL-10 cells and methods of using the polydonor CD4.sup.IL-10 cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, autoimmune and inflammatory diseases and other immune disorders.

The present disclosure features allogeneic modified cells (e.g., T- or NK-cells) having increased persistence, increased resistance to immune rejection, or decreased risk of eliciting a host-versus-graft reaction, or a combination thereof. Methods for producing and using the same are also provided.

The present disclosure provides modified cells including pluripotent stem cells, hematopoietic precursor cells, and hematopoietic cells (e.g., modified Tregs) that are steroid and/or calcineurin inhibitor-resistant. The present disclosure provides methods for generating steroid and/or calcineurin inhibitor-resistant modified cells including pluripotent stem cells, hematopoietic precursor cells, and hematopoietic cells. Also provided herein are compositions and methods of treatment.

The present invention relates to compositions and methods for generating a modified T cell with a nucleic acid capable of downregulating endogenous gene expression selected from the group consisting of TCR chain, TCR chain, beta-2 microglobulin, a HLA molecule, CTLA-4, PD1, and FAS and further comprising a nucleic acid encoding a modified T cell receptor (TCR) comprising affinity for a surface antigen on a target cell or an electroporated nucleic acid encoding a chimeric antigen receptor (CAR). Also included are methods and pharmaceutical compositions comprising the modified T cell for adoptive therapy and treating a condition, such as an autoimmune disease.

An isolated chimeric antigen receptor polypeptide (CAR), wherein the CAR comprises an extracellular antigen-binding domain, comprising an antibody or antibody fragment that binds a B Cell Maturation Antigen (BCMA) polypeptide. The CAR preferably binds an epitope comprising one or more amino acids of residues 13 to 32 of the N-terminus of human BCMA. Also disclosed is a nucleic acid molecule encoding the CAR of the invention, a genetically modified immune cell, preferably a T cell, expressing the CAR of the invention and the use of said cell in the treatment of a medical disorder associated with the presence of pathogenic B cells, such as a disease of plasma cells, memory B cells and/or mature B cells, in particular multiple myeloma, non-Hodgkin's lymphoma or autoantibody-dependent autoimmune diseases.

The present disclosure provides the use of fratricide-resistant chimeric antigen receptor T (CAR-T) cells targeting antigens expressed by T cell malignancies.

Described are methods of manufacturing engineered T cells and methods of using the engineered T cells to treat hematological malignancies. The engineered T cells can be administered in combination with allogeneic stem cell transplant and reduce the need for prophylactic immunosuppression.

This document provides methods and materials involved in treating a mammal (e.g., a human) having (or risk of developing) graft-versus-host disease (GVHD). For example, T cells (e.g., regulatory T cells) expressing one or more antigen receptors targeting one or more epithelial-specific antigens are provided. Also provided are methods for administering T-cells expressing one or more antigen receptors targeting one or more epithelial-specific antigens to a mammal having (or at risk of developing) GVHD to treat the GVHD.

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.

A method for engineering less alloreactive immune cells, including T-cells that express chimeric antigen receptors (CARs), using a nucleotide sequence in form of an RNA encoding a anti-TCR CAR to achieve the transient expression of anti-TCR CAR at the cell surface. The transient expression of the anti-TCR CAR recognized by the alpha beta TCR on the cell surface unexpectedly enabled the a purification of the TCR-negative CAR expressing cells. The TCR-negative CAR expressing immune cells can be used in adoptive therapy to treat diseases associated with cell surface antigens, such as cancer with less side effects, in particular less GVHD.