Biofunctionalized nanoparticles and uses thereof in adoptive cell therapy

Abstract

The present invention relates to biofunctionalized nanoparticles and uses thereof in adoptive cell therapy. In particular, the present invention relates to a nanoparticle comprising an amount of at least one antigen and an amount of at least one antibody having specificity for a B cell receptor wherein the antigen and antibody are attached to the surface of the nanoparticle.

1 . A nanoparticle comprising an amount of at least one antigen and an amount of at least one antibody having specificity for a B cell receptor wherein the antigen and antibody are attached to the surface of the nanoparticle. 
     
     
         2 . The nanoparticle of  claim 1  which is in the form of a sphere, needle, flake, platelet, tube, fiber, cube, prism, whiskers or which has an irregular shape and which is a mineral nanoparticle, is made of an organic polymer or is made of polysaccharides. 
     
     
         3 . The nanoparticle of  claim 1  wherein the at least one antigen is a viral antigen, a bacterial antigen, a fungal antigen, a protozoal antigen, a tumor-associated antigen, an auto-antigen, an allergen, a xenoantigen, an alloantigen, or a molecule that is exogenously administered for therapeutic or other purposes and may trigger an unwanted immune response. 
     
     
         4 . The nanoparticle of  claim 1  wherein the at least one antigen is a HLA molecule. 
     
     
         5 . The nanoparticle of  claim 1  wherein the antibody has specificity for the framework region of a kappa or lambda BCR light chain or for the framework region of a BCR heavy chain. 
     
     
         6 . The nanoparticle of  claim 1  wherein at least 2 or 3 anti-BCR antibodies are attached to the nanoparticles. 
     
     
         7 . A method for preparing a population of antigen-presenting B cells comprising incubating a population of B cells with an amount of the nanoparticles of  claim 1  for a time sufficient for allowing internalization of the nanoparticles into the B cells and isolating B cells that present the at least one antigen at their surface by MHCII molecules. 
     
     
         8 . The method of  claim 7  further comprising a step of conferring regulatory properties to said population of antigen-presenting B cells. 
     
     
         9 . A method for expanding a population of antigen-specific T helper cells comprising i) providing a population of the antigen-presenting B cells prepared according to the method of  claim 7  and ii) culturing a population of T cells in the presence of the population of the antigen presenting B cells of step i). 
     
     
         10 . The method of  claim 9  which further comprising a step of isolating the antigen-specific T helper cells. 
     
     
         11 . The method of  claim 9  further comprising a step of polarizing said population of antigen-specific T helper cells into a population of antigen-specific Th1, Th2 or Th17 cells. 
     
     
         12 . The method of  claim 9  further comprising a step of polarizing said population of antigen-specific T helper cells into a population of antigen-specific regulatory cells. 
     
     
         13 . A method of treating a cancer, an infectious disease, an autoimmune disease, an allergy, an immune reaction against a molecule that is exogenously administered for a therapeutic purpose or an immune reaction against a grafted tissue or grafted hematopoietic cells or grafted blood cells in a subject in need thereof comprising administering to the subject a therapeutically effective amount of
 the nanoparticles according to  claim 1 ,   a population of antigen-presenting B cells prepared by incubating B cells with an amount of the nanoparticles for a time sufficient to allow internalization of the nanoparticles into the B cells and isolating B cells that present the at least one antigen at their surface, or   a population of antigen-specific T cells prepared by culturing T cells in the presence of the antigen presenting B cells.