Peer-reviewed publication highlights advantages of Moditope® technology platform
Potential to develop completely new class of immuno-oncology therapeutics
Scancell Holdings plc, (‘Scancell’ or the ‘Company’) the developer of novel immunotherapies for the treatment of cancer, is pleased to announce the publication of an invited review in the scientific journal Autophagy entitled: “Autophagy, citrullination and cancer”, which describes Scancell’s pre-clinical data that supports the innovation and potential of the Company’s Moditope® platform1.
The review, whose lead author is Professor Lindy Durrant, Scancell’s Chief Scientific Officer, discusses the concept that citrullinated peptides produced during autophagy offer attractive vaccine targets for cancer therapy. Scancell’s Moditope® platform utilises this mechanism to stimulate the production of highly active CD4+ T cells that overcome self-tolerance and destroy tumour cells.
The data described in the review, and published in the peer-reviewed journal Cancer Research2, showed that a single immunization with Moditope® peptides, up to 14 days after tumour implant, resulted in long-term survival in up to 90% of mice, with no associated toxicity.
Professor Lindy Durrant, Chief Scientific Officer of Scancell commented:
“The interplay between autophagy, citrullination and cancer support the rationale behind our Moditope® platform technology. Moditope® has a unique mechanism of action that overcomes the immune suppression induced by tumour cells, allowing T cells to seek out and kill tumours that would otherwise be hidden from the immune system. We believe this platform has the potential to develop a new class of immuno-oncology therapeutics and look forward to progressing our first vaccine into the clinic as soon as possible.”
The first clinical trials of Modi-1, the lead candidate from the Moditiope® platform, are expected to target patients with triple negative breast cancer, ovarian cancer and osteosarcoma.
The full abstract of the review can be found below.
Autophagy, citrullination and cancer
A cell needs to maintain a balance between biosynthesis and degradation of cellular components to maintain homeostasis. There are 2 pathways, the proteasome, which degrades short-lived proteins, and the autophagy/lysosomal pathway, which degrades long-lived proteins and organelles. Both of these pathways are also involved in antigen presentation or the effective delivery of peptides to MHC molecules for presentation to T cells. Autophagy (macroautophagy) is a key player in providing substantial sources of citrullinated peptides for loading onto MHC-II molecules to stimulate CD4 T cell responses. Stressful conditions in the tumor microenvironment induce autophagy in cancer cells as a mechanism to promote their survival. We therefore investigated if citrullinated peptides could stimulate CD4 T cell responses that would recognize these modifications produced during autophagy within tumor cells. Focusing on the intermediate filament protein VIM (vimentin), we generated citrullinated VIM peptides for immunization experiments in
mice. Immunization with these peptides induced CD4 T cells in response to autophagic tumor targets. Remarkably, a single immunization with modified peptide, up to 14 days after tumor implant, resulted in long-term survival in 60% to 90% of animals with no associated toxicity. These results show how CD4 cells can mediate potent antitumor responses against modified self-epitopes presented on tumor cells, and they illustrate for the first time how the citrullinated peptides produced during autophagy may offer especially attractive vaccine targets for cancer therapy.
1. Lindy G. Durrant, Rachael L. Metheringham & Victoria A. Brentville (2016): Autophagy, citrullination and cancer, Autophagy, DOI: 10.1080/15548627.2016.1166326
2. Victoria A. Brentville, Rachael L. Metheringham, Barbara Gunn, Peter Symonds, Ian Daniels, Mohamed Gijon, Katherine Cook, Wei Zue & Lindy G Durrant (2015): Citrullinated vimentin presented on MHC-II in tumor cells is a target for CD4+ T cell-mediated autitumor immunity, Cancer Research 76(3), 548-560.
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Scancell is developing novel immunotherapies for the treatment of cancer based on its ImmunoBody® and Moditope® technology platforms.
Scancell’s first ImmunoBody®, SCIB1 is being developed for the treatment of melanoma. Data from the Phase 1/2 clinical trial demonstrate that SCIB1, when used as monotherapy, has a marked effect on tumour load, produces a melanoma-specific immune response and highly encouraging survival trend without serious side effects. In patients with resected disease there is increasing evidence to suggest that SCIB1 may delay or prevent disease recurrence.
Scancell’s ImmunoBody® vaccines target dendritic cells and stimulate both parts of the cellular immune system: the helper cell system where inflammation is stimulated at the tumour site and the cytotoxic T-lymphocyte or CTL response where immune system cells are primed to recognise and kill specific cells.
Pre-clinical data on a combination of SCIB1 or SCIB2 and checkpoint inhibition (blockade of the PD-1 or CTLA-4 immune checkpoint pathways) have shown enhanced tumour destruction and significantly longer survival times than when either treatment was used alone.
Scancell has also identified and patented a series of modified epitopes that stimulate the production of killer CD4+ T cells that destroy tumours without toxicity. The Directors believe that the Moditope® platform could play a major role in the development of safe and effective cancer immunotherapies in the future.