A methodology to obtain large numbers of allospecific human Tr1 lymphocytes in vitro differentiated with phenotype and suppressive function stability in presence of proinflammatory cytokines, by using donor tolerogenic dendritic cells (DC10) derived from donor monocytes and from a not related receptor (allogeneic) naîve T cells cocultures. The obtained cells with the present methodology are characterized by the expression of a Tr1 regulatory phenotype (CD4+, CD49b+, LAG-3+), being high IL-10 producers, and also they express additional co-inhibitory molecules as PD1, TIM-3, CD39, CTLA-4 y TIGIT. Moreover, the cellular product obtained by this methodology is able to maintain a stable phenotype and suppressive function in presence of proinflammatory cytokines (IL-1β, IL-6, IFN-γ y TNF-α). The numbers, purity, and stability of the Tr1 obtained by this methodology, make them great candidates for their use as therapeutic tools in transplantation.

Among the various aspects of the present disclosure is the provision of conditioning agents for use in allogeneic hematopoietic stem cell transplantation. An aspect of the present disclosure provides for a method of treating a subject or inhibiting alloreactivity in the host-versus-graft direction comprising administering a combination of conditioning agents comprising an anti-body-drug conjugate (ADC) and a JAK1/JAK2 inhibitor for use in allogeneic hematopoietic stem cell transplantation in an amount sufficient to permit engraftment of allogeneic bone marrow. In some embodiments, the JAK inhibitor is selected from baricitinib. In some embodiments, the method comprises administering a cancer therapeutic.

Disclosed herein are universal donor stem cells and related methods of their use and production. The universal donor stem cells disclosed herein are useful for overcoming the immune rejection in cell-based transplantation therapies. In certain embodiments, the universal donor stem cells disclosed herein do not express one or more MHC-I and MHC-II human leukocyte antigens. Similarly, in certain embodiments, the universal donor stem cells disclosed herein do not express one or more human leukocyte antigens (e.g., HLA-A, HLA-B and/or HLA-C) corresponding to MHC-I and MHC-II human leukocyte antigens, thereby rendering such cells hypoimmunogenic.

Compositions, reagents, formulations and methods to treat disease including autoimmune diseases and allergy are described. The compositions comprise an antigen causing immune intolerance, an immunosuppressant in a sustained release formulation. The methods, compositions, formulations and reagents to treat allergy also relate to applying the combination of allergen and immune activity enhancing agent in a sustained release formulation to a subject in need.

Compositions, reagents, formulations and methods to treat disease including autoimmune diseases and allergy are described. The compositions and formulations comprise an antigen causing immune intolerance, an immunosuppressant and a viscosity enhancing agent or a thermal phase changing agent. The reagent is a polymer conjugate comprising an antigen causing immune intolerance and an immunosuppressant conjugated to a polymer.

The present disclosure provides compositions for inducing immune tolerance and methods to modify antigen to treat allergy and autoimmune disease. Disclosed are compositions, and related methods, comprising APC presentable antigens and immunosuppressants that provide tolerogenic immune responses specific to antigen. In some embodiments, the composition is in a skin patch.

An isolated cell having a central memory T-lymphocyte (Tcm) phenotype, the cell being tolerance-inducing cell and capable of homing to the lymph nodes following transplantation, the cell being transduced to express a cell surface receptor comprising a T cell receptor signaling module is disclosed. Methods of generating same and using same are also disclosed.

Featured are cells and methods of use thereof for modulating an antigen-specific immune response in a subject. The cells comprise a set of transgenes comprising two or more of PD-L1, HLA-G or H2-M3, Cd47, Cd200, FASG or FasL, Ccl21 or Ccl21b, MfgeS and Serpin B9 or Spi6, that shield the cells from immune surveillance (ie. “cloaking genes”). The cells can be used to induce immune tolerance to an antigen (e.g., a donor alloantigen or a self-antigen), or to induce an immune response to (e.g., induce the production of antibodies directed against) a non-self antigen.

The invention describes a method and compounds for the prevention of immune responses towards allofactors, towards viral vectors used for gene therapy and gene vaccination, towards proteins to which subjects are naturally exposed, towards genetically-modified organisms and towards undesirable effects related to vaccine administration for allergic or infectious diseases.

Compositions and methods for inducing immune tolerance to proteins and subsequence administration of the proteins are disclosed. Compositions comprise proteins complexed with liposomes comprising PS and PC, wherein at least part of the PS is present as lyso-PS.