Cell therapy compositions comprising engineered human regulatory T cells (eTregs) characterized by ectopic overexpression of FOXP3 and Helios protein, produced via introduction of separate nucleic acid constructs respectively encoding FOXP3 and Helios (FOXP3+Helios+ eTregs). Cell therapy compositions comprising mixed populations of CD4+ and CD8+ Treg cells each with ectopic overexpression of FOXP3 and Helios. Methods of making and use the same for therapies involving inflammation and/or a disorder of the immune system.

Disclosed are a universal CAR-T cell knocking out one or more of CD3 delta, CD3 gamma, CD3 epsilon and CD3 zeta, and simultaneously introducing the HSV-TK gene. Also disclosed are a method for preparing the above-mentioned CAR-T cell, a preparation comprising the CAR-T cell, and the use of the CAR-T cell.

The invention provides methods and compositions for administration of allogeneic lymphocytes as an exogenous source of CD4+ T cell help for endogenous, tumor-reactive CD8+ T cells. Depletion of CD8+ T cells from the donor lymphocyte infusion reduces the risk of sustained engraftment and graft-versus-host disease. Removal of regulatory T cells from the infused population may augment the ability of non-regulatory T cells to provide help for endogenous effectors of anti-tumor immunity. Allogeneic T cell therapy is typically given in the context of allogeneic stem cell transplantation, in which the patient receives highly immunosuppressive conditioning followed by an infusion of a stem cell graft containing unselected populations of mature T cells. In the treatment described here, the graft is engineered to minimize the possibility of sustained donor cell engraftment, and the anti-tumor effector T cells derive from the host.

The present disclosure provides a population of poly-donor CD4.sup.IL-10 cells generated by genetically modifying CD.sup.4+ T cells from at least three different T cell donors. Further provided are methods of generating the poly-donor CD4.sup.IL-10 cells and methods of using the poly-donor CD4.sup.IL-10 cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, and other immune disorders.

According to the present disclosure, optimization of treatment for a rejection reaction by immune tolerance induction is provided.

According to the present disclosure, there is provided a method for evaluating quality of a medicament for achieving immune tolerance, which is administered to a patient who has undergone living-donor liver transplantation, the method including: (a) a step of mixing and culturing peripheral blood lymphocytes collected from a patient before the living-donor liver transplantation and peripheral blood lymphocytes collected from a donor of the living-donor liver transplantation; (b) a step of mixing and culturing peripheral blood lymphocytes collected from the patient before the living-donor liver transplantation, peripheral blood lymphocytes collected from the donor of the living-donor liver transplantation, and the medicament for achieving immune tolerance in the patient; and (c) a step of measuring cytokine production in steps (a) and (b), in which in a case where the cytokine production in step (b) has changed compared to step (a), the medicament is considered to be a medicament for immune tolerance therapy.

Methods, compositions, and kits for generating therapeutically relevant populations of immunosuppressive T-reg cells and uses thereof are disclosed.

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

A multi-chimeric cell created by ex vivo fusion of three or more hematopoietic stem cells, mesenchymal stem cells, myoblasts, pericytes, or satellite cells, or a combination thereof, from three or more different donors is provided, as is the use of these cells in transplant therapy and treatment of immune deficiency and genetic disorders.

The invention provides methods of using allogeneic cells in therapy by combining allogeneic cell therapy with anti-CD137 antibody drug conjugates (ADCs). Disclosed are methods of treating or preventing a host versus graft (HvG) rejection in a human subject receiving allogeneic cell therapy by administering to the human subject an anti-CD137 ADC.

The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.