A research team led by Prof. LIANG XingJie from the National Center for Nanoscience and Technology (NCNST) and Prof. LI Jinghong from Tsinghua University. proposed a new strategy for constructing transformable nanocarriers to improve antigen delivery and cancer vaccination. This study was published in “Nature nanotechnology”. Article link: https://www.nature.com/articles/s41565-020-00782-3.
Figure 1. Proton-driven transformable nanovaccine for cancer immunotherapy
Cancer vaccines hold great promise for improved cancer treatment. However, endosomal trapping and low immunogenicity of tumour antigens usually limit the efficiency of vaccination strategies.
Herein, scientists presented a proton-driven nanotransformer-based vaccine (NTV), comprising a polymer-peptide conjugate-based nanotransformer (NT) and loaded antigenic peptide (AP). NTV induces a strong immune response without significant systemic toxicity. In the acidic endosomal environment, NTV undergoes a dramatic morphological change from nanospheres (~100 nm in diameter) into nanosheets (several micrometers in length or width), which mechanically disrupts the endosomal membrane and directly delivers AP into the cytoplasm. The re-assembled nanosheets also boost tumour immunity via activation of specific inflammation pathways. NTV effectively inhibits tumour growth in B16F10-OVA and human papilloma virus-E6/E7 tumour models. Moreover, combining NTV with anti-PD-L1 antibodies results in over 83 days-survival and in about 50% complete tumour regression in the B16F10 model.
The proton-driven transformable nanovaccine may offer a robust and safe strategy for cancer immunotherapy.
This work was supported by the National Natural Science Foundation of China Key Project, National Key Research & Development Program of China and the Strategic Priority Research Program of the Chinese Academy of Sciences.
Figure 2. Transformable nanovaccine inhibits tumour growth and prolongs survival in a melanoma model