Targeted antigen delivery system and uses thereof
Disclosed are antigen delivery systems comprising a nanoparticle, wherein the nanoparticle is surface-modified with a cancer-specific cell targeting peptide and comprises an immunogenic HLA class I restricted peptide, wherein the HLA class I restricted peptide is a vaccine-dependent, immunogenic HLA class I restricted peptide; methods of treating a subject having cancer comprising administering said delivery systems; methods of killing cancer cells comprising contacting cancer cells delivery systems, wherein upon entry of the liposome into the cancer cells, the cancer cells present said peptide from said delivery system, wherein the cancer cells generate an immune response said peptide, and wherein the immune response to said peptide targets and kills the cancer cells presenting the vaccine-dependent, peptide; methods of generating a non-cancer secondary immune response that targets cancer cells comprising administering said delivery systems to a subject having cancer cells.
1 . An antigen delivery system comprising a PEGylated liposome, wherein the PEGylated liposome is surface-modified with a cancer-specific cell targeting peptide and comprises an immunogenic human leukocyte antigen (HLA) class I restricted peptide, wherein the HLA class I restricted peptide is a vaccine-dependent, immunogenic HLA class I restricted peptide that is encapsulated by the PEGylated liposome, and wherein the cancer-specific cell targeting peptide comprises a dimer comprising two targeting peptides each consisting of the sequence CH3CO-LQWRRNFGVWARYRL-PEG11 (SEQ ID NO: 1) and which are linked via PEG11 and a lysine branch point to form the sequence CH3CO-LQWRRNFGVWARYRL-PEG11-K-PEG11-LRYRAWVGFNRRWQL-CH3CO (SEQ ID NO: 3) on an external surface of the PEGylated liposome and which is configured to mediate internalization of the PEGylated liposome into a cancer cell and to facilitate presentation of the vaccine-dependent, immunogenic HLA class I restricted peptide, and wherein the antigen delivery system is an immunotherapeutic.
2 . The antigen delivery system of claim 1 , wherein the vaccine-dependent, immunogenic HLA class I restricted peptide is measles virus hemagglutinin peptide H250.
3 . The antigen delivery system of claim 1 , wherein the vaccine-dependent, immunogenic HLA class I restricted peptide is influenza virus hemagglutinin peptide HA.
4 . The antigen delivery system of claim 1 , wherein the vaccine- dependent, immunogenic HLA class I restricted peptide is smallpox virus H-2Kd-restricted vaccinia-specific peptide, A5275-83, which is VACV-A52.
5 . The antigen delivery system of claim 1 , wherein the vaccine-dependent, immunogenic HLA class I restricted peptide is selected from the group consisting of:
H250, which is SMYRVFEVGV (SEQ ID NO: 5);
C166, which is SLWGSLLML (SEQ ID NO: 6);
H38, which is LLAVIFVMFL (SEQ ID NO: 7);
H516, which is ILPGQDLQYV (SEQ ID NO: 8);
H3L, which is SLSAYIIRV (SEQ ID NO: 9);
E2L, which is KIDYYIPYV (SEQ ID NO: 10); and
01L, which is GLNDYLHSV (SEQ ID NO: 11).
6 . The antigen delivery system of claim 1 , wherein the antigen delivery system does not comprise any viral particles, toxins, or biologically-derived material.
7 . The antigen delivery system of claim 1 , wherein the cancer-specific cell targeting peptide is acetylated on the N-terminus.
8 . The antigen delivery system of claim 1 , wherein the cancer-specific cell targeting peptide comprises a PEG linker on the C-terminus.
9 . The antigen delivery system of claim 1 , wherein the dimer further comprises a conjugation moiety on the C-terminal side of the lysine branch point, wherein the conjugation moiety allows for conjugation to the liposome.