Immunostimulatory compositions and methods of use thereof
AssigneeMassachusetts Institute of Technology
InventorsDarrell Irvine, Haipeng Liu
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Abstract
Lipid conjugates for enhanced delivery of cargo to the lymph nodes are disclosed. The lipid conjugates typically include three domains: a lipophilic domain that binds to albumin, a polar block domain, and a cargo such as a molecular adjuvant or immunostimulatory compound (such as an oligonucleotide) or antigenic peptide. Depending on the cargo, the length and compositions of the polar block can be tailored to push the equilibrium toward albumin binding, stable micelle formation, or cell insertion. The conjugates can be administered to a subject, for example, a subject with cancer or an infection, to induce or enhance a robust immune response in the subject.
Claims31
An amphiphilic albumin-binding conjugate comprising
- (a) a lipid component;
- (b) an optional polar component;
- and
- (c) an immunomodulatory compound or molecular adjuvant;
- wherein the immunomodulatory compound or molecular adjuvant is bound directly to the lipid or is bound to the lipid via a linker,
- wherein the conjugate is sufficiently soluble such that the lipid binds to albumin under physiological conditions, and
- wherein a plurality of the conjugates can spontaneously form micelles in aqueous solution.
An oligonucleotide conjugate comprising an immunostimulatory oligonucleotide which is linked to a linker comprising at least 3 consecutive guanines which is conjugated to a lipid,
- wherein a plurality of the oligonucleotide conjugates can spontaneously form micelles in aqueous solution, and
- wherein more than 36% of the micelles are intact in the presence of 20% fetal bovine serum.
An amphiphilic peptide conjugate comprising an peptide antigen which
- (i) is conjugated directly to a lipid, or
- (ii) is linked to a linker which is conjugated to a lipid,
- wherein the lipid binds to albumin under physiological conditions,
- wherein the peptide antigen, the linker, or the peptide antigen and linker in combination are sufficiently polar to reduced or inhibit insertion of the lipid into a cell's plasma membrane.
Dependencies are inferred from the claim text.