Engineering Magnetosomes for High-Performance Cancer Vaccination

Abstract

A novel cancer vaccine is developed by using Fe 3 O 4 magnetic nanoclusters (MNCs) as the core and cancer cell membranes decorated with anti-CD205 as the cloak. Because of the superparamagnetism and magnetization of MNCs, it is first achieved for the magnetic retention of vaccine in the lymph nodes with a magnetic resonance imaging (MRI) guide, which opened the time window for antigen uptake by dendritic cells (DCs). Meanwhile, the camouflaged cancer cell membranes serve as a reservoir of various antigens, enabling subsequent multiantigenic response. Additionally, the decorated anti-CD205 direct more vaccine into CD8 + DCs, facilitating the major histocompatibility complex (MHC) I cross-presentation. These unique advantages together lead to a great proliferation of T cells with superior clonal diversity and cytotoxic activity. As a result, potent prophylactic and therapeutic effects with few abnormalities are observed on five different tumor models. Therefore, such a cancer-derived magnetosome with the integration of various recent nanotechnologies successfully demonstrates its promise for safe and high-performance cancer vaccination.

Advancements in prophylactic and therapeutic nanovaccines

“…Toll-like receptor (TLR) agonist (CpG) loaded Fe 3 O 4 magnetic nanoclusters camouflaged with cancer membrane and was decorated with anti-CD205 for preferential recognition by CD8 + DC population for cross-presentation to CD8 + T cells via MHC-I. Enhanced stimulation of tumor-specific CD8 + T cells due to prolonged retention of magnetically guided nanocluster in lymph nodes showed anti-tumor efficacy with improved survival in different mice models [191] . Similarly, Guo et al, developed an erythrocyte membrane coated PLGA nanoparticle-containing hgp10025-33 antigenic peptide and monophosphoryl lipid-A (MPL-A) TLR-4 agonist for enhanced anti-tumor immunity.…”

Recent Advances in Particulate Adjuvants for Cancer Vaccination

“…On the other hand, particulate adjuvants also present great potential to move across the extracellular matrix and target lymph nodes along the lymphatic circulation, which can directly activate APCs in their resident sites. Kuai and coworkers developed a nanodisc containing antigen peptides and CpG, which could effectively reach lymph nodes and activate CD8 T cell responses 4b. Furthermore, several approaches can be applied to further extend the retention of these vaccines at the injection site or lymph nodes for APC recruitment and activation, such as hydrogel or magnetic control, enhancing the efficacy of the elicited immune response 4a,77…”

“…In addition, considering the large number of molecules and receptors (such as mannose receptors, CD205,4a and other molecules) distributed around the APC surface, decorating with the corresponding ligands (such as mannose, anti‐CD205 antibodies, and other molecules) presents a potential to further promote APC uptake. Li and coworkers developed an engineered magnetosome as a high‐performance cancer vaccine, which was modified with anti‐CD205 antibodies, promoting recognition and uptake by CD8 + DCs and thus enhancing the CD8 T cell responses 4a. Furthermore, many physicochemical features of particulate adjuvants, including surface potential, polarity, and other features, also affect APC uptake.…”

“…After subcutaneous or intramuscular injections, these vaccines can generate an antigen reservoir, called the depot effect, to recruit and activate APCs, and the activated APCs then home to lymph nodes ( Figure ) . In addition, vaccines can also directly reach lymph nodes through the lymphatic circulation, activating resident APCs . Then, the activated APCs in the lymph nodes can present antigens via major histocompatibility complex (MHC) I or MHC II molecules, activating CD8 T cells or CD4 T cells into efficiently expanded cytotoxic T lymphocytes (CTLs) or helper T cells (Th) cells (including Th1 cells and Th2 cells), respectively .…”

“…Generally, cancer‐derived macromolecules such as proteins, peptides, nucleic acids, or polysaccharides can be utilized as cancer‐associated antigens for cancer vaccination 4b,6. However, despite high injection doses and multiple administrations, their behaviors in cancer vaccination have been less successful than anticipated .…”