Abstract: Compositions and methods are provided for the achievement of organ and tissue transplantation and autoimmune tolerance using the infusion of living and/or deceased donor hematopoietic cells. The methods provided herein provide for conditioning with a plurality of doses of total lymphoid irradiation (TLI), and a single, very low dose of TBI (svldTBI), referred to herein as “TLI-svldTBI-ATG” or “TLI-svldTBI” depending on whether ATG is included. The combination of svldTBI and TLI specifically targets non-lymphoid-tissue resident memory immune cells. An in vitro manipulated donor cell composition is provided for use with the conditioning regimen, in which specific ratios of CD34+ and other hematopoietic stem cell and precursor cell populations are combined with defined doses of CD3+ T cells, and/or purified regulatory T cells (Treg) cells, invariant natural killer (iNK-T) cells, and/or CD8+ memory T cells.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to an HLA mismatched recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Residual, refractory or relapsed cancer is treated by immunostimulation in the presence of allogeneic immune effector cells, optimally in combination with radiation therapy. The methods of the disclosure induce a systemic allogeneic anti-tumor immune response that results in tumor regression in untreated sites of disease, i.e. non-injected, non-irradiated, etc.

Abstract: Residual, refractory or relapsed cancer is treated by immunostimulation in the presence of allogeneic immune effector cells, optimally in combination with radiation therapy. The methods of the disclosure induce a systemic allogeneic anti-tumor immune response that results in tumor regression in untreated sites of disease, i.e. non-injected, non-irradiated, etc.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to an HLA mismatched recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Residual, refractory or relapsed cancer is treated by immunostimulation in the presence of allogeneic immune effector cells, optimally in combination with radiation therapy. The methods of the disclosure induce a systemic allogeneic anti-tumor immune response that results in tumor regression in untreated sites of disease, i.e. non-injected, non-irradiated, etc.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to a recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to an HLA mismatched recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: Residual, refractory or relapsed cancer is treated by immunostimulation in the presence of allogeneic immune effector cells, optimally in combination with radiation therapy. The methods of the disclosure induce a systemic allogeneic anti-tumor immune response that results in tumor regression in untreated sites of disease, i.e. non-injected, non-irradiated, etc.