Ganglioside-KLH conjugate vaccine plus QS-21
AssigneeSloan-Kettering Institute for Cancer Research
InventorsPhilip Ordway Livingston, Friedhelm Helling
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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.
Claims17
A composition which comprises:
- (a) a conjugate of (i) a derivative of a ganglioside, which ganglioside is a GM2, GD2, GD3 lactone, O-acetyl GD3, or GT3 ganglioside and comprises an unaltered sphingosine base, wherein the derivative differs from the ganglioside solely by having an altered sphingosine base which retains only C1 through C4 from the unaltered sphingosine base of the ganglioside, and (ii) Keyhole Limpet Hemocyanin, wherein the 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 E-aminolysyl group of Keyhole Limpet Hemocyanin;
- (b) QS-21;
- and
- (c) a pharmaceutically acceptable carrier,
- wherein the amount of the conjugated ganglioside derivative is an amount between about 1 μg and about 200 μg, the amount of QS-21 is an amount between about 10 μg and about 200 μg, the ganglioside derivative:
- Keyhole Limpet Hemocyanin molar ratio is from 200:1 to 1400:
- 1, and the relative amounts of such conjugate and QS-21 is effective to stimulate or enhance production in a subject of an antibody to the ganglioside.
A method of stimulating or enhancing production of an antibody to GM2, GD2, GD3 lactone, O-acetyl GD3, and GT3 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 ganglioside, which ganglioside is a GM2, GD2, GD3 lactone, O-acetyl GD3, or GT3 ganglioside and comprises an unaltered sphingosine base, wherein the derivative differs from the ganglioside solely by having an altered sphingosine base which retains only C1 through C4 from the unaltered sphingosine base of the ganglioside, and (ii) Keyhole Limpet Hemocyanin, wherein the 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) QS-21;
- and
- (c) a pharmaceutically acceptable carrier,
- wherein the amount of the conjugated ganglioside derivative is an amount between about 1 μg and about 200 μg, the amount of QS-21 is an amount between about 10 μg and about 200 μg, and the ganglioside derivative:
- Keyhole Limpet Hemocyanin molar ratio is from 200:1 to 1400:
- 1, and the relative amounts of such conjugate and QS-21 is effective to stimulate or enhance production in a subject of an antibody to the ganglioside.
A method of treating a human subject having a cancer which comprises administering to the subject an effective cancer-treating amount of a composition which comprises:
- (a) a conjugate of (i) a derivative of a ganglioside, which ganglioside is a GM2, GD2, GD3 lactone, O-acetyl GD3, or GT3 ganglioside and comprises an unaltered sphingosine base, wherein the derivative differs from the ganglioside solely by having an altered sphingosine base which retains only C1 through C4 from the unaltered sphingosine base of the ganglioside, and (ii) Keyhole Limpet Hemocyanin, wherein the 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) QS-21;
- and
- (c) a pharmaceutically acceptable carrier,
- wherein the amount of the conjugated ganglioside derivative is an amount between about 1 μg and about 200 μg, the amount of QS-21 is an amount between about 10 μg and about 200 μg, the ganglioside derivative:
- Keyhole Limpet Hemocyanin molar ratio is from 200:1 to 1400:
- 1, and the relative amounts of such conjugate and QS-21 is effective to stimulate or enhance production in a subject of an antibody to the ganglioside.
Dependencies are inferred from the claim text.