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Paramyxoviruses for Tumor-targeted Immunomodulation: Design and Evaluation Ex Vivo
Published on: January 7, 2019
Hit-and-run vaccine system that overcomes limited neoantigen epitopes for efficient broad antitumor response
Hongyu Chen1, Zichao Huang1, Jiaxuan Li2
1School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China; Key laboratory of Polymer Ecomaterials, Changchun Institue of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
Abstract:
Neoantigen cancer vaccines have been envisioned as one of the most promising means for cancer therapies. However, identifying neoantigens for tumor types with low tumor mutation burdens continues to limit the effectiveness of neoantigen vaccines. Herein, we proposed a "hit-and-run" vaccine strategy which primes T cells to attack tumor cells decorated with exogenous "neo-antigens". This vaccine strategy utilizes a peptide nanovaccine to elicit antigen-specific T cell responses after tumor-specific decoration with a nanocarrier containing the same peptide antigens. We demonstrated that a poly(2-oxazoline)s (POx) conjugated with OVA257-264 peptide through a matrix metalloprotease 2 (MMP-2) sensitive linker could efficiently and selectively decorate tumor cells with OVA peptides in vivo. Then, a POx-based nanovaccine containing OVA257-264 peptides to elicit OVA-specific T cell responses was designed. In combination with this hit-and-run vaccine system, an effective vaccine therapy was demonstrated across tumor types even without OVA antigen expression. This approach provides a promising and uniform vaccine strategy against tumors with a low tumor mutation burden.
Insights
This study introduces a novel "hit-and-run" cancer vaccine strategy. This approach effectively targets tumors with low mutation burdens by decorating cancer cells with neoantigens, enhancing T cell responses for improved cancer therapy.
Area of Science:
- Oncology
- Immunology
- Nanotechnology
- Biomedical Engineering
Background:
- Neoantigen cancer vaccines show promise but are limited in tumors with low mutation burdens.
- Developing effective cancer therapies for these challenging tumor types remains a critical unmet need.
Purpose of the Study:
- To propose and validate a "hit-and-run" vaccine strategy for treating tumors with low tumor mutation burdens.
- To demonstrate the efficacy of a peptide nanovaccine system that elicits T cell responses against tumor cells decorated with exogenous neoantigens.
Main Methods:
- Utilized a poly(2-oxazoline)s (POx)-based nanocarrier conjugated with OVA257-264 peptide via an MMP-2 sensitive linker for tumor cell decoration.
- Developed a POx-based nanovaccine containing OVA257-264 peptides to induce OVA-specific T cell responses.
- Evaluated the therapeutic effectiveness of the combined "hit-and-run" vaccine system in preclinical models.
Main Results:
- Demonstrated efficient and selective in vivo decoration of tumor cells with OVA peptides using the POx-nanocarrier system.
- Successfully elicited OVA-specific T cell responses using the designed nanovaccine.
- Showcased effective vaccine therapy across various tumor types, including those lacking endogenous OVA antigen expression.
Conclusions:
- The "hit-and-run" vaccine strategy offers a promising and uniform approach for cancer therapy, particularly in tumors with low mutation burdens.
- This novel nanovaccine system overcomes limitations of traditional neoantigen vaccines by enabling targeted antigen delivery and T cell priming.
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