Lipid-conjugated rhamnose for immune system recruitment and oncotherapy
L-Rhamnose antigen-lipid conjugates for recruitment of the immune system to sites of tumor growth for initiating an anti-tumor antigen response. Methods for introducing L-rhamnose antigen-conjugated lipids into cell membranes such that L-rhamnose antigens are displayed on the cell surface. The cells can be tumor cells and more specifically can be melanoma cells. Cells are contacted with one or more L-rhamnose antigen-lipid conjugates such that L-rhamnose antigen-lipid conjugates are inserted into the cell membrane. The cells can be contacted for example by intratumoral injection. Pharmaceutical compositions containing the L-rhamnose antigen-lipid conjugates and therapeutic methods employing the conjugates and compositions.
1. A lipid conjugate of formula:
where:
both of s and t are 0, both of s and t are 1, or one of s or t is 0, and the other of s or t is 1;
Me is a methyl group;
R 5 and R 6 are independently selected from alkyl or monounsaturated alkenyl groups having 12-18 carbon atoms; and
L 1 is —(CH 2 ) a-b —, where a+b is 4-6.
2. A pharmaceutical composition comprising a therapeutically effective amount of one or more lipid conjugates of claim 1 and a pharmaceutically acceptable carrier.
3. The pharmaceutical composition of claim 2 further comprising one or more antibodies, and/or one or more antigen lipid conjugates where the antigen is other than L-rhamnose antigen and/or one or more non-conjugated lipids which can facilitate insertion of antigen-lipid conjugates into cell membranes.
4. The pharmaceutical composition of claim 2 , wherein the lipid conjugate is formed into a lipid aggregate selected from a vesicle, a bilayer, a micelle, a liposome or a mixture thereof.
5. A method for treating melanoma in an individual in need of treatment thereof and which individual has endogenous anti-rhamnose antibodies which comprises administering a therapeutically effective amount of a lipid conjugate of claim 1 or a pharmaceutical composition comprising said lipid conjugate to a melanoma tumor cell such that the cell is labeled with anti-rhamnose antigen.
6. The method of claim 5 , wherein administration comprises intratumoral injection.
7. The method of claim 5 , wherein administration is by intradermal injection.
8. A lipid conjugate of claim 1 of formula:
where Me is a methyl group, and R 5 and R 6 are alkyl or monounsaturated alkenyl groups having 12-18 carbon atoms.
9. The lipid conjugate of claim 8 , wherein R 5 and R 6 are monounsaturated alkenyl groups having 12-18 carbon atoms.
10. The lipid conjugate of claim 9 of formula:
where Me is a methyl group.
11. The lipid conjugate of claim 1 , wherein both L 1 are —(CH 2 ) 4 —.
12. A pharmaceutical composition comprising a therapeutically effective amount of one or more lipid conjugates of claim 8 and a pharmaceutically acceptable carrier.
13. The pharmaceutical composition of claim 12 further comprising one or more antibodies, and/or one or more antigen lipid conjugates where the antigen is other than L-rhamnose antigen and/or one or more non-conjugated lipids which can facilitate insertion of antigen-lipid conjugates into cell membranes.
14. The pharmaceutical composition of claim 13 , wherein the lipid conjugate is formed into a lipid aggregate selected from a vesicle, a bilayer, a micelle, a liposome or a mixture thereof.