Technology Overview

The treatment of many cancers is being revolutionised by immunotherapies such as the checkpoint inhibitors Keytruda® (Merck; pembrolizumab) and Opdivo® (Bristol-Myers Squibb; nivolumab). Although these therapies can improve the long-term survival of cancer patients, only a minority of patients with certain types of cancers respond and there is no benefit at all in patients with other types of cancers. The challenge to immuno-oncology is therefore to improve the proportion of patients that respond well to therapy.

Vaccination is a well-established method for the prevention of diseases and has proven to be particularly effective as a prophylactic treatment against many viruses. The development of cancer vaccines to treat cancer have been more challenging. The main goal is to increase the activity of the immune response against tumour cells and this requires the induction of high-avidity, cytotoxic T cells. This in turn requires the careful selection of cancer antigens or epitopes (short amino acid sequences that make up part of the protein) and an effective delivery mechanism.

Since the outbreak of the COVID-19 pandemic, several groups have initiated programmes to produce a vaccine. The vast majority of these have focused on generating virus-neutralising antibodies (VNAbs) and not on stimulating high avidity T cell responses; importantly, the latter have been shown to correlate with mild disease in China. In contrast, our aim is to produce a simple, cost effective and scalable vaccine that gives durable T cell responses plus VNAbs, potentially conferring better protection in the long-term.

The first of Scancell’s technology platforms to be developed, ImmunoBody®, is designed to induce potent cytotoxic CD8 T cell responses against multiple epitopes via a unique dual-mechanism of action to stimulate a broad anti-tumour effect. They are DNA vaccines that encode a protein in the form of a modified antibody, which is engineered to express epitopes from a cancer antigen whilst retaining the ability to target activated antigen presenting cells in vivo. The potent immune responses induced by ImmunoBody® vaccines have been shown to result in long term survival in melanoma patients treated with Scancell’s first ImmunoBody® vaccine, SCIB1.

Scancell’s second platform, Moditope®, is a completely novel concept based on stress-induced post translational modifications (siPTMs). The technology exploits and harnesses the normal immune response that utilises cytotoxic CD4 T cells to eradicate stressed cells. Tumour cells are, by nature, stressed due to their rapid growth and lack of oxygen and nutrients. By identifying these stress-induced modifications, Scancell has been able to design modified peptide vaccines which induce potent T cells that seek and destroy tumour cells.

The Moditope® platform also provides a pathway for the potential development of CD4-based T cell receptor (TCR) therapies, whereby T cells recognising siPTMs could be utilised for adoptive cell transfer. With most of the current approaches focused on CD8-based TCRs, the ability to isolate CD4-TCRs recognising these novel cancer targets opens up a new window of opportunity for Scancell’s Moditope® technology.

 

Scancell‘s third platform focuses on anti-glycan antibodies that recognise and directly kill cancer cells without the need for involvement of the complement system or immune accessory cells. Glycans are co-accessory molecules involved in regulation of many physiological processes and inhibition of these leads to rapid cell death. They therefore represent ideal targets for novel cancer therapeutics as they are aberrantly over-expressed by tumours compared to normal tissues, and monoclonal antibodies (mAbs) binding to them results in tumour destruction. The platform includes Fc modification technology which produces antibodies that can self-associate upon target recognition and results in potent, high avidity mAbs. This technology (AvidiMab™) has been used to confer the direct killing ability of mouse anti-glycan antibodies to human antibodies and could be used to increase the efficacy of any antibody.

Scancell plans to use its proven cancer vaccine concept to design a vaccine against SARS-CoV-2, the virus that causes COVID-19. We have designed a DNA vaccine to stimulate high avidity T cells and give durable responses, ultimately leading to better protection. In addition to the receptor binding domain of the spike protein, Scancell’s vaccine also targets the nucleoprotein, which is highly conserved amongst coronaviruses. This vaccine may therefore also confer protection against new emerging coronaviruses that may evolve in the future.