Conformation-Transformable, Spiked Polypeptide Enables In Situ Cancer Vaccination via Conditional Antigen Capture and...

Area of Science:

• Biomaterials Science
• Immunology
• Nanotechnology

Background:

• Autologous tumor antigen cancer vaccines show promise for immunotherapy.
• Current vaccines face challenges in antigen capture efficiency and cancer-selective immune activation.

Purpose of the Study:

• To develop a self-adjuvanted vaccine precursor that forms an in situ cancer vaccine.
• To engineer conformation-transformable polypeptides for conditional antigen capture and STING activation.

Main Methods:

• Constructed mesoporous silica nanoparticles (MSN) encapsulated with melittin and decorated with DMXAA-conjugated polypeptides.
• Utilized conformation transformation of polypeptides in the tumor microenvironment to trigger melittin release and antigen capture.
• Achieved STING (stimulator of interferon genes) activation via polyvalent DMXAA display.

Main Results:

• The vaccine precursor adopted a dormant, flexible conformation, preventing premature antigen capture.
• In the acidic tumor microenvironment, polypeptides formed rigid helical structures, releasing melittin to kill cancer cells and generate antigens.
• The in situ nanovaccine demonstrated effective antigen capture and STING activation, leading to robust antitumor immunity.
• Significant inhibition of tumor growth and recurrence was observed in B16F10 tumor-bearing mice.

Conclusions:

• Developed a conformation-transformable, self-adjuvanted vaccine precursor for in situ cancer vaccination.
• Demonstrated a novel design strategy controlling polymer conformation for regulating biomacromolecule interactions.
• This approach offers a promising paradigm for personalized cancer vaccine development.