Method for tumor treatment using infusion of xenogeneic cells to induce hyperacute rejection and innocent bystander effect

Abstract

A method for treating tumors. Through infusion or xenotransplantation of xenogeneic cells, such as infusion of murine cells into the peritoneal cavity of humans, a hyperacute rejection response to the cells is induced. This in turn creates a bystander effect to the tumor. This effect creates tumor regression. This treatment can be used alone or in conjunction with gene therapy or chemotherapy treatments.

1 . A method for treating a solid tumor in an αGal (−)  mammal, having anti-αGal antibodies, said method comprising: 
 administering to said mammal at or near said tumor, an effective amount of cells having an α(1,3) galactosyl epitope to activate a local hyperacute rejection, wherein said cells are other than vector producing cells.    
     
     
         2 . The method of  claim 1 , wherein the tumor is in the peritoneal cavity.  
     
     
         3 . The method of  claim 1  where the αGal (−)  mammal is a human.  
     
     
         4 . The method of  claim 1  where the cells having an aGal epitope are of xenogeneic origin, obtained from an αGal (+)  mammal.  
     
     
         5 . The method of  claim 4  where said mammal is of murine origin.  
     
     
         6 . The method of  claim 4  where said cells are from murine origin.  
     
     
         7 . The method of  claim 1  where αGal (+)  cells are human cells obtained by introduction of a polynucleotide sequence expressing the alpha(1,3) galactosyltransferase gene.  
     
     
         8 . The method of  claim 7  where the alpha(1,3) galactosyltransferase gene is from murine origin  
     
     
         9 . A method for treating a solid tumor in a human, the method comprising: 
 administering at or near said tumor an effective amount of cells having an α(1,3) galactosyl epitope, said cells being characterized in that they do not have a functional retroviral gag gene wherein said cells activate a hyperacute rejection response thereby inhibiting the growth of a tumor in said human.    
     
     
         10 . The method of  claim 9 , wherein the tumor is in the peritoneal cavity.  
     
     
         11 . The method of  claim 9  where the cells having aGal epitopes are of xenogeneic origin, obtained from an αGal (+)  mammal.  
     
     
         12 . The method of  claim 11  where such mammal is of murine origin.  
     
     
         13 . The method of  claim 11  where such cells are from murine origin.  
     
     
         14 . The method of  claim 9  where αGal (+)  cells are human cells obtained by introduction of a polynucleotide sequence expressing the alpha(1,3) galactosyltransferase gene.  
     
     
         15 . The method of  claim 14  where the alpha(1,3) galactosyltransferase gene is from murine origin  
     
     
         16 . A method for inhibiting the growth of a solid tumor in a human having anti-αGal antibodies, the method comprising: 
 delivering into or near the tumor an effective amount of a xenogeneic cell that expresses an α (1,3) galactosyl epitope and that does not produce retroviral proteins thereby causing a local hyperacute rejection response against said xenogeneic cell and a bystander immune reaction against the tumor thereby inhibiting the growth of the tumor in the subject.    
     
     
         17 . A method of inhibiting the growth of a solid tumor in a human subject, the method comprising: 
 administering to said subject into or near the tumor an effective amount of xenogeneic cells containing an α(1,3)galactosyl epitope and which do not produce retroviral virions, in order to activate a hyperacute rejection response thereby inhibiting the growth of said tumor.    
     
     
         18 . A method for activating an immune response against a solid tumor in a human subject, the method comprising: 
 administering to said subject into or near the tumor an effective amount of xenogeneic cells containing an α(1,3)galactosyl epitope and which do not produce retroviral virions, without subsequent administration of ganciclovir, where said xenogeneic cells activate an immune response against said tumor.    
     
     
         19 . A method for inhibiting growth of a solid tumor in an animal with pre-existing anti-alpha Gal antibodies comprising: 
 administering to said animal, into or near the tumor, an effective amount of xenogeneic cells containing an α (1,3) galactosyl epitope and which do not contain a tumor specific antigen specific for said solid tumor, to generate a localized hyperacute rejection response near to said solid tumor to inhibit the growth of said tumor.    
     
     
         20 . A method for eliciting an immune response against tumor specific antigens which are present within a solid tumor in an animal with pre-existing anti-alpha Gal antibodies comprising: 
 administering to said animal, into or near the tumor, an effective amount of xenogeneic cells containing an α (1,3) galactosyl epitope and which do not generate retroviral virions, to create a localized hyperacute rejection response near said solid tumor and a concomitant immune response against tumor specific antigens within said solid tumor thereby inhibiting the growth of said tumor    
     
     
         21 . The method of  claim 20  wherein said xenogeneic cells do not contain a tumor specific antigen for said solid tumor in said animal.  
     
     
         22 . A method for eliciting an immune response against tumor specific antigens which are present within a solid tumor in an animal with pre-existing anti-alpha Gal antibodies comprising: 
 administering to said animal an effective amount of xenogeneic cells containing an α(1,3) galactosyl epitope and which do not contain said tumor specific antigen for said solid tumor and do not generate retroviral particles, to create a localized hyperacute rejection response near said solid tumor thereby inhibiting the growth of said tumor    
     
     
         23 . A pharmaceutical composition to inhibit the growth of a solid tumor in a human subject, said composition comprising αGal (+)  cells which do not contain a tumor specific antigen present in said tumor.  
     
     
         24 . The composition of  claim 23  where such cells are αGal (+)  cells of murine origin.  
     
     
         25 . The composition of  claim 23  where such cells are human cells obtained by introduction of a polynucleotide sequence directing the expression of an alpha(1,3) galactosyltransferase gene.  
     
     
         26 . The composition of  claim 25  where such alpha(1,3) galactosyltransferase gene is of murine origin.  
     
     
         27 . The composition of  claim 26  wherein said cells are inactivated.  
     
     
         28 . The composition of  claim 23  wherein said αGal (+)  cells are inactivated by ultraviolet, gamma or X irradiation.  
     
     
         29 . The composition of  claim 23  wherein said cells do not contain a retroviral nucleotide sequence.  
     
     
         30 . The composition of  claim 23  wherein said cells do not contain a functional gag gene.  
     
     
         31 . The method of  claim 23  wherein said cells do not produce retroviral proteins.  
     
     
         32 . The method of  claim 23  wherein said cells are other than vector producing cells.  
     
     
         33 . A method for eliciting an immune response against tumor specific antigens which are present within a solid tumor in an animal with pre-existing anti-alpha Gal antibodies comprising: 
 administering to said animal an effective amount of xenogeneic cells containing an α (1,3) galactosyl epitope and which do not contain predetermined tumor specific antigens for said solid tumor and do not generate retroviral particles, to create a localized hyperacute rejection response near said solid tumor and an immune response to said tumor