Abstract
The unsatisfactory response rate of immune checkpoint blockade (ICB) immunotherapy severely limits its clinical application as a tumor therapy. Here, we generate a vaccine-based nanosystem by integrating siRNA for Cd274 into the commercial human papillomavirus (HPV) L1 (HPV16 L1) protein. This nanosystem has good biosafety and enhances the therapeutic response rate of anti-tumor immunotherapy. The HPV16 L1 protein activates innate immunity through the type I interferon pathway and exhibits an efficient anti-cancer effect when cooperating with ICB therapy. For both resectable and unresectable breast tumors, the nanosystem decreases 71% tumor recurrence and extends progression-free survival by 67%. Most importantly, the nanosystem successfully induces high response rates in various genetically modified breast cancer models with different antigen loads. The strong immune stimulation elicited by this vaccine-based nanosystem might constitute an approach to significantly improve current ICB immunotherapy.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents, Immunological / therapeutic use*
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B7-H1 Antigen / antagonists & inhibitors
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B7-H1 Antigen / genetics
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Breast Neoplasms / genetics
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Breast Neoplasms / immunology
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Breast Neoplasms / therapy*
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Cancer Vaccines / administration & dosage*
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Cancer Vaccines / genetics
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Cancer Vaccines / immunology
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Capsid Proteins / genetics
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Capsid Proteins / immunology
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Cell Line, Tumor / transplantation
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Disease Models, Animal
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Female
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Gene Knockdown Techniques
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HEK293 Cells
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Human papillomavirus 16 / genetics
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Human papillomavirus 16 / immunology
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Humans
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Immunity, Innate / genetics
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Immunotherapy / methods*
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Mice
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Nanoparticles / administration & dosage*
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Neoplasm Recurrence, Local
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Oncogene Proteins, Viral / genetics
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Oncogene Proteins, Viral / immunology
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Progression-Free Survival
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RNA, Small Interfering / genetics
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / genetics
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Tumor Microenvironment / genetics
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Tumor Microenvironment / immunology
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Vaccines, Synthetic / administration & dosage
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Vaccines, Synthetic / genetics
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Vaccines, Synthetic / immunology
Substances
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Antineoplastic Agents, Immunological
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B7-H1 Antigen
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Cancer Vaccines
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Capsid Proteins
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Cd274 protein, mouse
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Oncogene Proteins, Viral
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RNA, Small Interfering
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Recombinant Proteins
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Vaccines, Synthetic
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L1 protein, Human papillomavirus type 16