Targeted antigen delivery system and uses thereof
Inventors
Brown, Kathlynn C. • McGuire, Michael J. • Venugopal, Indu
Assignees
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Publication Number
US-12636378-B2
Publication Date
2026-05-26
Expiration Date
Abstract
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.
Core Innovation
The invention provides an antigen delivery system that is an immunotherapeutic and comprises a PEGylated liposome. 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 that is a vaccine-dependent, immunogenic HLA class I restricted peptide encapsulated by the PEGylated liposome.
The cancer-specific cell targeting peptide 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. The cell targeting peptide comprises a dimer in which two targeting peptides each consist of the sequence CH3CO-LQWRRNFGVWARYRL-PEG11 (SEQ ID NO:1), 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.
The disclosed system targets cancer-cell internalization to promote autophagy-mediated antigen processing and HLA class I presentation, thereby enabling CD8+ T-cell-dependent cytotoxicity. The patent also describes using a targeting peptide with a more stable optimized form derived from a less stable parent sequence, and specifies PEGylated stealth features, dimer structure, and N-terminal acetylation. Documented results include improved binding/solubility and reduced off-target localization, with co-localization with autophagic vesicles and cytokine induction in HLA-matched co-culture.
Claims Coverage
The provided independent claim covers one inventive concept centered on a PEGylated liposome immunotherapeutic with a cancer-specific dimeric cell targeting peptide and an encapsulated vaccine-dependent immunogenic HLA class I restricted peptide.
PEGylated liposome immunotherapeutic with encapsulated HLA class I peptide
An antigen delivery system comprising a PEGylated liposome, wherein the PEGylated liposome comprises an immunogenic human leukocyte antigen (HLA) class I restricted peptide that is a vaccine-dependent, immunogenic HLA class I restricted peptide encapsulated by the PEGylated liposome, and wherein the antigen delivery system is an immunotherapeutic.
Surface-modified cancer-specific dimer targeting peptide
The PEGylated liposome is surface-modified with a cancer-specific cell targeting peptide, 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).
Dimer linkage via PEG11 and lysine branch point on external liposome surface
The two targeting peptides 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.
Internalization to facilitate HLA class I presentation
The cancer-specific cell targeting peptide 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.
The inventive coverage centers on a PEGylated liposome immunotherapeutic that encapsulates a vaccine-dependent immunogenic HLA class I restricted peptide and displays a structurally defined cancer-specific dimeric targeting peptide to mediate cancer-cell internalization and facilitate HLA class I presentation.
Stated Advantages
Enhance cancer-cell internalization.
Facilitate presentation of the vaccine-dependent, immunogenic HLA class I restricted peptide.
Enable CD8+ T-cell-dependent cytotoxicity.
Improve binding/solubility and reduce off-target localization.
Enhance co-localization with autophagic vesicles.
Induce cytokines TNF-α and IFN-γ in HLA-matched co-culture with CD8 dependence.
Reduce tumor burden in orthotopic/syngeneic lung and other tumor models using luciferase imaging.
Documented Applications
Orthotopic/syngeneic lung cancer model using luciferase imaging.
Other tumor models evaluated with luciferase imaging.
HLA-matched co-culture of immune cells to evaluate CD8 dependence and induction of TNF-α and IFN-γ.
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