Compositions and methodology for delivery of alpha-galactosylceramide compounds

Abstract

Compositions and methods are described for treating a disease, such as cancer or a viral or bacterial infection. More specifically, the provided compositions comprise encapsulated CD1d-restricted invariant Natural Killer T cell antigen, a bacterial α-galactosylceramide.

Description

Compositions and methods for treating diseases such as cancer, viral infections, or bacterial infections are described. More specifically, the provided compositions comprise encapsulated CD1d-restricted constant natural killer T-cell antigen, a bacterial α-galactosylceramide. Abstract

Claims

Atty. Dkt. No.060348-0802 WHAT IS CLAIMED IS:

1. A composition comprising: (a) a pharmaceutically acceptable carrier; and (b) a plurality of delivery elements selected from intact bacterially derived minicells, intact killed bacterial cells, intact mammalian cells, and extracellular vesicles, the delivery elements comprising an α-galactosylceramide compound that: (i) comprises (i) a N-acyl chain of 16 to 17 carbons in length and (ii) a hydroxyl group on the β- rather than the α-carbon; and (ii) does not present a 4-hydroxy group on its sphingoid base, wherein the compound can form a CD1d-lipid-TCR trimeric complex in vivo such that iNKT cells are activated.

2. The composition of claim 1, wherein the compound further comprises (iii) an iso- branched lipid terminus.

3. The composition of claim 1 or claim 2, wherein at least some of the delivery elements are mammalian cells selected from the group consisting of natural killer cells, dendritic cells, and macrophages.

4. The composition of claim 1 or claim 2, wherein at least some of the delivery elements are intact bacterially derived minicells.

5. The composition of claim 1 or claim 2, wherein at least some of the delivery elements are extracellular vesicles.

6. The composition of any of claims 1-5, wherein the compound was purified to pharmaceutical grade after in vitro expression thereof by commensal bacteria.

7. The composition of claim 6, wherein the compound was purified to a level in a range from 97% to 99%. -53- 4889-3769-4391.1Atty. Dkt. No.060348-0802 8. The composition of claim 6 or claim 7, wherein the bacterium is selected from the group consisting of Bacteroides fragilis, Bacteroides vulgatus, and Prevotella copri.

9. The composition of claim 8, wherein the bacterium is Bacteroides fragilis.

10. The composition of claim 9, wherein the compound is α-GalCerBf.

11. A dosage form comprising a single-use vial that comprises about 1 x 1010to about 1 x 1011minicells packaged with an α-GalCer compound as recited in claim 1, such that the vial comprises a therapeutically effective dose of the compound.

12. A method of treating or vaccinating against a viral or bacterial infection, comprising administering to a subject in need of such treating or vaccinating a therapeutically effective amount of a composition according to any one of claims 1 – 10.

13. A method of treating cancer, comprising administering to a subject who suffers from a cancer pathology a therapeutically effective amount of a composition according to any one of claims 1 – 10. -54- 4889-3769-4391.1

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