A New Frontier<br /> in Immuno-Oncology

A New Frontier
in Immuno-Oncology

Scancell is focused on developing 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.

Antibody collaboration deal for Scancell

CEO Cliff Holloway tells Proactive London why its antibody collaboration deal is significant and details how it complements Scancell's existing antibody technology. He also explains what is unique about Scancell's antibody pipeline.

T cell repertoire to citrullinated self-peptides in healthy humans is not confirmed to the HLA-DR SE alleles; Targeting of citrullinated self-peptides presented by HLA-DP4 for tumour therapy

T cell repertoire to citrullinated self-peptides in healthy humans is not confirmed to the HLA-DR SE alleles; Targeting of citrullinated self-peptides presented by HLA-DP4 for tumour therapy

Victoria A Brentville, Peter Symonds, Katherine  W Cook, Ian Daniels, Tracy Pitt, Mohamed Gijon, Poonam Vaghela, Wei Xue, Sabaria Shah, Rachael E Metheringham, and Lindy Durrant

ABSTRACT: Post-translational modifications are induced in stressed cells which cause them to be recognised by the system. One such modification is citrullination where the positive charged arginine is modified to a neutral citrulline. We demonstrate most healthy donors show an oligoclonal CD4 response in vitro to at least one citrullinated vimentin or enolase peptide. Unlike rheumatoid arthritis patients, these T cell responses were not restricted by HLA-DRB1 shared epitope (SE) alleles, suggesting they could be presented by other MHC class II alleles. As HLA-DP is less polymorphic than HLA-DR, we investigated whether the common allele, HLA-DP4 could present citrullinated epitopes. The modification of arginine to citrulline enhanced binding of the peptides to HLA-DP4 and enhanced high-frequency CD4 responses in HLA-DP4 transgenic mouse models. Our previous studies have shown that tumours present citrullinated peptides restricted through HLA-DR4 which are good target for anti-tumour immunity. In this study, we show that citrullinated vimentin and enolase peptides also induced strong anti-tumour immunity (100% survival, p < 0.0001) against established B16 tumours d and against the LLC/2 lung cancer model (p = 0.034) both expressing HLA-DP4. Since most tumours do not constitutively express MHC class II molecules, models were engineered that expressed MHC class II under the control of an IFNγ inducible promoter. Immunisation with citrullinated peptides resulted in 90% survival (p < 0.001) against established B16 HHD tumour expressing IFNγ inducible DP4. These studies show that citrullinated peptides can be presented by a range of MHC class II molecules, including for the first time HLA-DP4, and are strong targets for anti-tumour immunity.

CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, Paris, 25-28 September 2019

Post-translationally modified antigens are good targets for cancer immunotherapy but some patients have antigen specific T-regs that may need to be neutralized

Suha Atabani, Victoria Brentville, Ian Daniels, Ruhul Choudhury, Katherine Cook, Poulam Patel and Lindy Durrant

Improving selection criteria for post translationally modified CD4 epitopes using computer algorithms.

K Cook, P Symonds, A Skinner, S Shah, R Metheringham, S Paston, V Brentville and L Durrant

Carbamylation of lysine residues mediated by MDSCs in the tumour environment make excellent targets for CD4 T cell mediated cancer immunotherapy

K Cook, W Xue, I Daniels, P Symonds, M Gijon, D Boocock, C Coveney, A Miles, P Vaghela, R Choudhury, S Shah, S Atabani, R Metheringham, V Brentville and L Durrant

Targeting citrullinated vimentin and enolase with cytotoxic CD4 T cells, relies upon MHC-II expression by tumors, reduces myeloid suppressor cells and directly kills tumor cells

V Brentville, R Metheringham, I Daniels, S Atabani, P Symonds, K Cook, R Choudhury, P Vaghela, M Gijon, G Meiners, W-J Krebber, CJM Melief and L Durrant

Citrullinated glucose-regulated protein 78 is a candidate target for cancer immunotherapy

V Brentville, J Chua, S Atabani, P Symonds, K Cook, R Choudhury, I Daniels, S Shah and L Durrant

An ultraspecificmonoclonal antibody recognises a novel marker on stem memory T cells and induce cell proliferation and differentiation in vitro and in vivo

J Chua, E Cid, M Vankemmelbeke, R McIntosh, R Metheringham, I Daniels, V Brentville and L Durrant