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Virus‐like particles for vaccination against cancer

Advanced Review

Mona O. Mohsen, Daniel E. Speiser, Alexander Knuth, Martin F. Bachmann

Published Online: Aug 27 2019

DOI: 10.1002/wnan.1579

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Abstract Active immunotherapy of cancer aims to treat the disease by inducing effective cellular and humoral immune responses. Virus‐like particle‐based vaccines have evolved dramatically over the last few decades, greatly reducing morbidity and mortality of several infectious diseases and expectedly preventing cervical cancer caused by human papilloma virus. In contrast to these broad successes of disease prevention, therapeutic cancer vaccines remain to demonstrate clinical benefit. Yet, several preclinical and clinical trials have revealed promising results and are paving the way for medical breakthroughs. This study reviews and discusses the recent preclinical development and clinical trials in this field. This article is categorized under: Biology‐Inspired Nanomaterials > Protein and Virus‐Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Virus‐like particle (VLP)‐based vaccines and the induction of B cell responses. The highly organized and repetitive surface geometry of a VLP‐based vaccine (1) facilitates its opsonization and phagocytosis by antigen‐presenting cells (2) as well as the engagement of CD21 on B cells (3). B cells also interact with and receive help from T_H cells subsequent to uptake of VLP‐based vaccines via B cell receptor (4). This interaction between T_H CD4⁺ T cells and B cells are essential for efficient generation of Ab‐producing plasma cells as well as for memory B cells (5). Many VLPs carry RNA packaged during production engaging TLR7/8 in B cells, promoting isotype‐switching towards protective T_H1 IgG subclasses which will cause tumor cell destruction (6)

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Virus‐like particle (VLP)‐based vaccines and the induction of T cell responses. Following injection, a VLP‐based vaccine is taken up by dendritic cells and macrophages (1). The phagocytosed VLPs displaying the tumor antigen will be processed and presented on both MHC‐II (2) and MHC‐I (3) for recognition by CD4⁺ and CD8⁺ T cells, respectively. Naïve CD8⁺ T cells will proliferate and differentiate into various types of effector and memory cytotoxic T‐lymphocyte (CTLs) (4). CTLs will initiate the killing process of tumor cells (5). Effector CD4⁺ T_H1 cells enhance antigen presentation by antigen‐presenting cells and assist activated CTLs (6)

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A sketch illustrating some key characteristics of virus‐like particles (VLPs) as an efficient vaccine platform

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Virus‐like particle (VLP)‐based vaccines against cervical cancer. (a) A sketch illustrates human papilloma virus (HPV) VLP‐based vaccines: (1) VLP‐E7 was based on cloning the C‐terminal region of HPV‐E7 epitope “45–98” excluding the oncogenic domain OD to the C‐terminal of VP2 of IBDV‐VLP, while (2) VLP‐E7‐B was generated by inserting the HPV‐E7 epitope into the VP2 protein. (b) (1) E7 oligomers “50 nm” chemically coupled to Qβ‐VLPs “25–30 nm” using SMPH cross‐linker and loaded with nonmethylated CpGs, (2) E7 oligomers admixed with Qβ‐VLPs loaded with CpGs

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Virus‐like particle (VLP)‐based vaccines against breast cancer. (a) A schematic diagram of the structure of the HER‐2 receptor. The extracellular part consists of four domains: Domain I, Domain II (CR1), Domain III and Domain IV (CR2). The other domains are single transmembrane domain, juxtra membrane domain, tyrosine‐kinase domain and finally a C‐terminal tail. (b) SpyTag/SpyCatcher VLP‐based vaccine based on displaying the subdomains I–IV of HER‐2 combined to SyCatcher covalently attached to AP205‐VLP outer surface fused to a SpyTag part

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Virus‐like particle (VLP)‐based vaccines against melanoma. (a) (1) Ovalbumin (OVA_257–264) nonself epitope was fused to the C terminus of VP1 major coat protein of polyomavirus forming polyoma‐like particles of ~45 nm. (2) Tyrosinase‐related protein 2 (TRP2_180–188) self‐epitope was fused to VP1 major coat protein forming polyoma‐like pentamers of ~9 nm. (b) Mix multi‐target VLP‐based vaccine consisting of germline and mutated CTL epitopes coupled to Qβ‐VLPs by Cu‐free click chemistry and loaded with B‐type CpGs (Mohsen, Vogel, et al., ). (c) A microcrystalline tyrosine crystal decorated with CuMV_TT‐p33 nanoparticles labeled with AF488 (Mohsen, Heath, et al., )

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Vaccines in the context of check‐point inhibitors. Cancer immunotherapy targets immune checkpoints that regulates and inhibits the immune system. Monoclonal antibodies targeting (1) CTLA4 molecules on Tregs, for example, Ipilimumab (2) PD‐1 on T cells, for example, Nivolumab or Pembrolizumb (3) PDL‐1 on myeloid cells or/and tumor cells, for example, Atezolizumab have been approved by The food and drug administration (FDA) and are currently used in the clinics for treating different solid tumors. Combining a VLP‐based vaccine with checkpoint inhibitor is an optimal strategy to augment the immune response

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