Ganglioside-KLH conjugate vaccine with QS-21

Abstract

This invention provides a vaccine for stimulating or enhancing in a subject to which the vaccine is administered, production of an antibody which recognizes a ganglioside, comprising an amount of ganglioside or oligosaccharide portion thereof conjugated to an immunogenic protein effective to stimulate or enhance antibody production in the subject, an effective amount of adjuvant and a pharmaceutically acceptable vehicle.

1 - 43 . (canceled)  
   
   
       44 . A composition which comprises: 
 a) a conjugate of (i) a derivative of a GM2 ganglioside, which GM2 ganglioside comprises an unaltered sphingosine base, wherein the derivative differs from the GM2 ganglioside solely by having an altered sphingosine base which retains only C1 through C4 from the unaltered sphingosine base of the GM2 ganglioside, and (ii) Keyhole Limpet Hemocyanin, wherein the GM2 ganglioside derivative is covalently bound to Keyhole Limpet Hemocyanin by a stable amine bond between the C-4 carbon of the altered sphingosine base and a nitrogen of an ε-aminolysyl group of Keyhole Limpet Hemocyanin;    b) a saponin; and    c) a pharmaceutically acceptable carrier,    wherein the amount of the conjugated GM2 ganglioside derivative is an amount between about 1 μg and about 200 μg, the amount of the saponin is an amount between about 10 μg and about 200 μg, and the GM2:Keyhole Limpet Hemocyanin molar ratio is from 200:1 to 1400:1, the relative amounts of the conjugate and of the saponin being effective to stimulate or enhance production in a subject of an antibody to the GM2 ganglioside.    
   
   
       45 . A method of treating a subject afflicted with a cancer which comprises administering to the subject an amount of the composition of  claim 44  effective to stimulate or enhance production in a subject of an antibody to the GM2 ganglioside and to thereby treat the cancer in the subject.  
   
   
       46 . A method of stimulating or enhancing production of an antibody directed to the GM2 ganglioside in a subject which comprises administering to the subject an effective amount of a composition which comprises: 
 a) a conjugate of (i) a derivative of a GM2 ganglioside, which GM2 ganglioside comprises an unaltered sphingosine base, wherein the derivative differs from the GM2 ganglioside solely by having an altered sphingosine base which retains only C1 through C4 from the unaltered sphingosine base of the GM2 ganglioside, and (ii) Keyhole Limpet Hemocyanin, wherein the GM2 ganglioside derivative is covalently bound to Keyhole Limpet Hemocyanin by a stable amine bond between the C-4 carbon of the altered sphingosine base and a nitrogen of an ε-aminolysyl group of Keyhole Limpet Hemocyanin;    b) a saponin; and    c) a pharmaceutically acceptable carrier,    wherein the amount of the conjugated GM2 ganglioside derivative is an amount between about 1 μg and about 200 μg, the amount of the saponin is an amount between about 10 μg and about 200 μg, and the GM2:Keyhole Limpet Hemocyanin molar ratio is from 200:1 to 1400:1, the relative amounts of the conjugate and of the saponin being effective to stimulate or enhance production in a subject of an antibody directed to the GM2 ganglioside.    
   
   
       47 . A method of treating a human subject having cancer which comprises administering to the subject an effective amount of a composition which comprises: 
 a) a conjugate of (i) a derivative of a GM2 ganglioside which GM2 ganglioside comprises an unaltered sphingosine base, wherein the derivative differs from the GM2 ganglioside solely by having an altered sphingosine base which retains only C1 through C4 from the unaltered sphingosine base of the GM2 ganglioside, and (ii) Keyhole Limpet Hemocyanin, wherein the GM2 ganglioside derivative is covalently bound to Keyhole Limpet Hemocyanin by a stable amine bond between the C-4 carbon of the altered sphingosine base and a nitrogen of an ε-aminolysyl group of Keyhole Limpet Hemocyanin; and    b) a saponin; and    c) a pharmaceutically acceptable carrier,    wherein the amount of the conjugated GM2 ganglioside derivative is an amount between about 1 μg and about 200 μg, the amount of saponin is an amount between about 10 μg and about 200 μg, the GM2 derivative:Keyhole Limpet Hemocyanin molar ratio is from 200:1 to 1400:1, the relative amounts of the conjugate and of the saponin being effective to stimulate or enhance production in a subject of an antibody to the GM2 ganglioside and thereby treat the subject.