A New Frontier<br /> in Immuno-Oncology

A New Frontier
in Immuno-Oncology

Scancell's primary focus is to develop innovative immunotherapies for cancer that stimulate the body’s own immune system. A key challenge in the fight against cancer is that many tumours successfully evade the body’s own natural defences. Scancell’s mission is to overcome this by developing products that stimulate the immune system to treat or prevent cancer.

The field of immuno-oncology is now established as a significant weapon in the war against cancer, driven largely by the approval of immune checkpoint inhibitors. However, checkpoint inhibitors alone are not effective in most patients and so there is still an urgent need to identify optimum treatment combinations and/or develop new classes of therapies to improve the lives of millions of people with cancer. Scancell’s goal is to develop new classes of competitive ‘off the shelf’ therapeutics that are applicable to a broad range of patients with the aim to improve overall response and address the many unmet needs in the treatment of cancer.

Scancell has identified several differentiated approaches to cancer immunotherapy. Moditope® is a completely novel class of cancer vaccines, which is based on stress-induced post translational modifications (siPTMs). Alongside its ImmunoBody® platform, these two technologies provide complementary immune modulation mechanisms capable of stimulating potent CD4 and CD8 T cell responses that can effectively identify, target and kill cancer cells. Moditope® also provides a new pathway for the potential development of CD4-based T cell receptor (TCR) therapy. In addition, Scancell’s anti-glycan antibody platform AvidiMab™ provides a third method of attack against overexpressed tumour targets.

In response to the COVID-19 pandemic, Scancell has turned its clinical expertise in cancer to produce a simple, safe, cost-effective and scalable vaccine to induce both durable T cell responses and virus neutralising antibodies against SARS-Cov-2, the virus that causes COVID-19. The Company believes this combined T cell and antibody approach should give more potent and long-lasting responses, ultimately leading to better protection.

Cancer Vaccines, Adjuvants, and Delivery Systems

Cancer Vaccines, Adjuvants, and Delivery Systems

Samantha J. Paston, Victoria A. Brentville, Peter Symonds and Lindy G. Durrant

ABSTRACT: Vaccination was first pioneered in the 18th century by Edward Jenner and eventually led to the development of the smallpox vaccine and subsequently the eradication of smallpox. The impact of vaccination to prevent infectious diseases has been outstanding with many infections being prevented and a significant decrease in mortality worldwide. Cancer vaccines aim to clear active disease instead of aiming to prevent disease, the only exception being the recently approved vaccine that prevents cancers caused by the Human Papillomavirus. The development of therapeutic cancer vaccines has been disappointing with many early cancer vaccines that showed promise in preclinical models often failing to translate into efficacy in the clinic. In this review we provide an overview of the current vaccine platforms, adjuvants and delivery systems that are currently being investigated or have been approved. With the advent of immune checkpoint inhibitors, we also review the potential of these to be used with cancer vaccines to improve efficacy and help to overcome the immune suppressive tumor microenvironment.

 

Combination vaccine based on citrullinated vimentin and enolase peptides induces potent CD4-mediated anti-tumor responses

Combination vaccine based on citrullinated vimentin and enolase peptides induces potent CD4-mediated anti-tumor response

Victoria A Brentville, Rachael L Metheringham, Ian Daniels, Suha Atabani, Peter Symonds, Katherine W Cook, Mireille Vankemmelbeke, Ruhul Choudhury, Poonam Vaghela, Mohamed Gijon, Ghislaine Meiners, Willem-Jan Krebber, Cornelis J M Melief, Lindy G Durrant

ABSTRACT: Background  Stress-induced post-translational modifications occur during autophagy and can result in generation of new epitopes and immune recognition. One such modification is the conversion of arginine to citrulline by peptidylarginine deiminase enzymes.

Engineering the human Fc-region enables direct cell killing by cancer glycan-targeting antibodies without the need for immune effector cells or complement

Fc-engineering cytotoxicity in cancer glycan-targeting mAbs

Engineering the human Fc-region enables direct cell killing by cancer glycan-targeting antibodies without the need for immune effector cells or complement

Mireille Vankemmelbeke, Richard S. McIntosh, Jia Xin Chua, Thomas Kirk, Ian Daniels, Marilena Patsalidou, Robert Moss, Tina Parsons, David Scott, Gemma Harris, Judith M. Ramage, Ian Spendlove and Lindy G. Durrant

ABSTRACT: Murine IgG3 glycan-targeting mAb often induces direct cell killing in the absence of immune effector cells or complement via a proinflammatory mechanism resembling oncotic necrosis. This cancer cell killing is due to non-covalent association between Fc regions of neighboring antibodies, resulting in enhanced avidity. Human isotypes do not contain the residues underlying this cooperative binding mode; consequently, the direct cell killing of mouse IgG3 mAb is lost upon chimerization or humanization. Using the Lewisa/c/x -targeting 88mAb, we identified the murine IgG3 residues underlying the direct cell killing and increased avidity via a series of constant region shuffling and subdomain swapping approaches to create improved ('i') chimeric mAb with enhanced tumor killing in vitro and in vivo. Constant region shuffling identified a major CH3 and a minor CH2 contribution, which was further mapped to discontinuous regions among residues 286-306 and 339-378 that, when introduced in 88hIgG1, recapitulated the direct cell killing and avidity of 88mIgG3. Of greater interest was the creation of a sialyl-di-Lewisa -targeting i129G1 mAb via introduction of these selected residues into 129hIgG1, converting it into a direct cell killing mAb with enhanced avidity and significant in vivo tumor control. The human iG1 mAb, termed Avidimabs, retained effector functions, paving the way for the proinflammatory direct cell killing to promote ADCC and CDC through relief of immunosuppression. Ultimately, Fc engineering of human glycan-targeting IgG1 mAb confers proinflammatory direct cell killing and enhanced avidity, an approach that could be used to improve the avidity of other mAb with therapeutic potential.