Immunogenic compositions containing N-glycolylneuraminic acid bearing nanoparticles
The present invention provides an active cancer vaccine and specifically an immunogenic compositions of membrane vesicles that serve as biomimetic nanoparticles derived from eukaryotic cell membranes that bear N-glycolylneuraminic acid glycoconjugates. These compositions can elicit beneficial immunological responses for treatment of Neu5Gc-positive tumors. The present invention provides methods of generating and using Neu5Gc-conjugated nanoparticles from eukaryotic cells membranes designated nano-ghosts.
1 . An immunogenic composition comprising a plurality of membrane vesicles bearing N-glycolylneuraminic acid (Neu5Gc) glycoconjugates;
wherein the Neu5Gc glycoconjugates are exposed on the outer surface of the membrane vesicles;
wherein said membrane vesicles are cell ghosts derived from the outer plasma membrane of a porcine Ggta1 −/− red blood cell expressing Neu5Gc; and
wherein the membrane vesicles have an average hydrodynamic diameter in the submicron range.
2 . The immunogenic composition according to claim 1 , wherein the average hydrodynamic diameter of the membrane vesicles is within the range of 30-1000 nm.
3 . The immunogenic composition according to claim 1 , further comprising at least one additional tumor-associated antigen, wherein the at least one additional tumor-associated antigen is exposed on the outer surface of the membrane vesicle.
4 . The immunogenic composition according to claim 1 , further comprising an adjuvant approved for human use.
5 . A vaccine comprising the immunogenic composition according to claim 1 .
6 . A method of stimulating an anti-cancer immune response in a subject, the method comprising administering the vaccine of claim 1 to the subject.
7 . The method according to claim 6 , wherein the cancer is Neu5Gc-positive.
8 . The method according to claim 6 , comprising repeated administrations.
9 . The method according to claim 6 , further comprising administering an additional immunotherapeutic drug to the subject.
10 . The method according to claim 9 , wherein the vaccine and the additional immunotherapeutic drug are administered substantially simultaneously, concurrently, alternately, successively or according to overlapping schedules.
11 . The method according to claim 9 , wherein the additional immunotherapeutic drug is an immune checkpoint inhibitor.
12 . The method according to claim 11 , wherein the immune checkpoint inhibitor is selected from PD-1 inhibitor, PD-L1 inhibitor and CTLA-4 inhibitor.