Virus-like particle display of HER2 induces potent anti-cancer responses

Abstract

Overexpression of human epidermal growth factor receptor-2 (HER2) occurs in 20–30% of invasive breast cancers. Monoclonal antibody therapy is effective in treating HER2-driven mammary carcinomas, but its utility is limited by high costs, side effects and development of resistance. Active vaccination may represent a safer, more effective and cheaper alternative, although the induction of strong and durable autoantibody responses is hampered by immune-tolerogenic mechanisms. Using a novel virus-like particle (VLP) based vaccine platform we show that directional, high-density display of human HER2 on the surface of VLPs, allows induction of therapeutically potent anti-HER2 autoantibody responses. Prophylactic vaccination reduced spontaneous development of mammary carcinomas by 50%-100% in human HER2 transgenic mice and inhibited the growth of HER2-positive tumors implanted in wild-type mice. The HER2-VLP vaccine shows promise as a new cost-effective modality for prevention and treatment of HER2-positive cancer. The VLP platform may represent an effective tool for development of vaccines against other non-communicable diseases.

Virus‐like particles for vaccination against cancer

“…The results revealed that the vaccine significantly hampered the growth of the established tumors and prevented pulmonary metastases (Bolli et al, 2018). Palladini et al (2018) have designed a unique VLP-based vaccine allowing a directional and high-density display of the full extracellular domain of HER-2 (subdomain I-IV) on the surface of AP205-VLPs. The developed vaccine is based on a SpyTag/SpyCatcher conjugation system where HER-2 antigen was genetically fused to the SpyCatcher sequence which is attached to the surface of AP205-VLPs expressing the "SpyTag" (Figure 6b).…”

Immunization with virus-like particles conjugated to CIDRα1 domain of Plasmodium falciparum erythrocyte membrane protein 1 induces inhibitory antibodies

“…Vaccines presenting antigens on Virus-Like Particles (VLP) have been shown to induce high tittered, long lasting functional IgG responses in humans [29,30] and can drive immune responses even to weakly immunogenic or self-antgens [31,32]. We, and others, have recently developed a technique that allows effective coupling of complex proteins to pre-formed VLP and demonstrated that the IgG response to the proteins coupled is potent, functional, and durable even with self-antigens [31,33,34]. Here, VLP-CIDRα1.4 vaccines adjuvanted with aluminum hydroxide elicited stronger immune responses than a similar soluble CIDRα1 vaccine in Freund's incomplete adjuvant, and antibodies reactive and functionally inhibitory across group A CIDRα1 variants was elicited from immunization with a single CIDRα1 antigen variant.…”

Virus-Like Particles as an Instrument of Vaccine Production

“…This system is already utilized to design different types of vaccines, including the vaccines against tuberculosis and malaria [84,85]. A recent report has demonstrated that it was successfully used to develop a vaccine against breast cancer [86]. This work is remarkable due to the fact that the high density of the HER2 antigen (human epidermal factor receptor 2) synthesized in the cultured Drosophila melanogaster cells could be obtained on the AP204 VLP surface [32].…”

“…This work is remarkable due to the fact that the high density of the HER2 antigen (human epidermal factor receptor 2) synthesized in the cultured Drosophila melanogaster cells could be obtained on the AP204 VLP surface [32]. The obtained particles induced a strong immune response to the antigen in the patients, which rendered it possible to overcome the immune tolerance to HER2 known for patients with the HER2-dependent breast cancer [85,86].…”

“…Vaccine against breast cancer (HER2 antigen presentation). It is also implemented to develop vaccines against malaria and tuberculosis [82][83][84][85][86] The use of VLPs for vaccination in medicine is becoming increasingly widespread. This point is reinforced by the list of clinical trials of VLP vaccines prepared by the United States National Institute of Health.…”