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Recombinant ferritin-based nanoparticles as neoantigen carriers significantly inhibit tumor growth and metastasis
Wei Zheng1, Shixiong Li1, Zhongliang Shi1
1State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Protein Sciences, Cancer Biology Center, College of Life Sciences, Nankai University, Tianjin, 300071, PR China.
Background:
Tumor neoantigen peptide-based vaccines, systemic immunotherapies that enhance antitumor immunity by activating and expanding antigen-specific T cells, have achieved remarkable results in the treatment of a variety of solid tumors. However, how to effectively deliver neoantigens to induce robust antitumor immune responses remains a major obstacle.
Results:
Here, we developed a safe and effective neoantigen peptide delivery system (neoantigen-ferritin nanoparticles, neoantigen-FNs) that successfully achieved effective lymph node targeting and induced robust antitumor immune responses. The genetically engineered self-assembled particles neoantigen-FNs with a size of 12 nm were obtained by fusing a neoantigen with optimized ferritin, which rapidly drainage to and continuously accumulate in lymph nodes. The neoantigen-FNs vaccine induced a greater quantity and quality of antigen-specific CD8+ T cells and resulted in significant growth control of multiple tumors, dramatic inhibition of melanoma metastasis and regression of established tumors. In addition, no obvious toxic side effects were detected in the various models, indicating the high safety of optimized ferritin as a vaccine carrier.
Conclusions:
Homogeneous and safe neoantigen-FNs could be a very promising system for neoantigen peptide delivery because of their ability to efficiently drainage to lymph nodes and induce efficient antitumor immune responses.
Insights
This study presents a novel neoantigen-ferritin nanoparticle (neoantigen-FNs) delivery system for cancer vaccines. Neoantigen-FNs effectively target lymph nodes, enhancing T cell responses and controlling tumor growth with high safety.
Area of Science:
- Nanotechnology
- Immunology
- Vaccine Development
Background:
- Neoantigen peptide-based vaccines show promise for solid tumors by boosting T cell immunity.
- Effective delivery of neoantigens to induce strong antitumor responses remains a challenge.
Purpose of the Study:
- To develop a safe and effective delivery system for neoantigens.
- To enhance lymph node targeting and subsequent antitumor immune responses.
Main Methods:
- Genetically engineered self-assembled neoantigen-ferritin nanoparticles (neoantigen-FNs) were created by fusing neoantigens with ferritin.
- The 12 nm neoantigen-FNs were designed for rapid lymph node drainage and accumulation.
Main Results:
- Neoantigen-FNs achieved efficient lymph node targeting and induced robust antitumor immune responses.
- The vaccine generated a higher quantity and quality of antigen-specific CD8+ T cells.
- Significant tumor growth control, melanoma metastasis inhibition, and established tumor regression were observed.
- No obvious toxic side effects were detected, indicating high safety.
Conclusions:
- Homogeneous and safe neoantigen-FNs are a promising system for neoantigen peptide delivery.
- The system efficiently drains to lymph nodes, inducing potent antitumor immune responses.
