Bioengineered Nanocage from HBc Protein for Combination Cancer Immunotherapy

Abstract

Protein nanocages are promising multifunctional platforms for nanomedicine owing to the ability to decorate their surfaces with multiple functionalities through genetic and/or chemical modification to achieve desired properties for therapeutic and diagnostic purposes. Here, we describe a model antigen (OVA peptide) that was conjugated to the surface of a naturally occurring hepatitis B core protein nanocage (HBc NC) by genetic modification. The engineered OVA-HBc nanocages (OVA-HBc NCs), displaying high density repetitive array of epitopes in a limited space by self-assembling into symmetrical structure, not only can induce bone marrow derived dendritic cells (BMDC) maturation effectively but also can be enriched in the draining lymph nodes. Nai ̈ve C57BL/6 mice immunized with OVA-HBc NCs are able to generate significant and specific cytotoxic T lymphocyte (CTL) responses. Moreover, OVA-HBc NCs as a robust nanovaccine can trigger preventive antitumor immunity and significantly delay tumor growth. When combined with a low-dose chemotherapy drug (paclitaxel), OVA-HBc NCs could specifically inhibit progression of an established tumor. Our findings support HBc-based nanocages with modularity and scalability as an attractive nanoplatform for combination cancer immunotherapy.

Multifunctional biomolecule nanostructures for cancer therapy

“…Nanostructures derived from caged proteins are well suited for cancer immunotherapy owing to their geometries and surface properties, which are similar to viruses 192 – 194 . As vaccine platforms and natural adjuvants, these nanostructures promote passive localization of tumour antigens in the lymphatic system, endocytosis of antigens by APCs and antigen presentation to adaptive immune cells 162 , 163 .…”

Enhancing the Efficacy of Tumor Vaccines Based on Immune Evasion Mechanisms

“…First, nanoparticles can be loaded with different adjuvants and molecules, making them novel vectors for different types of tumor vaccines, such as peptide vaccines, RNA vaccines ( 75 , 76 ). Molecules such as chemical drugs and immune checkpoint inhibitors can be loaded into the vectors with the vaccines to achieve synergistic antitumor effects.…”

Tubule-specific protein nanocages potentiate targeted renal fibrosis therapy

“…We next tried to develop virus-mimetic protein nanoparticles derived from HBc NCs for targeting delivery of CLT. HBc NC is the most flexible and promising model for medical research among various types of protein NCs [20,21]. To trigger exceptional renal specificity at high accumulation rates, we generated the K3-HBc NCs by inserting K3 peptide (flanked by two glycine-rich flexible linkers) into the surface-exposed spike of HBc NC, and used E. coli as a natural bio-factory to produce bioengineered K3-HBc proteins.…”