Moditope® citrullinated peptides stimulate potent anti-tumour responses

Scancell Holdings Plc, (AIM:SCLP), today announced the publication, on line, of a full paper in Cancer Research describing the rationale behind the Company’s Moditope® platform and the experimental results that support it.1 Cancer Research is the official journal of the American Association for Cancer Research and is one of the world’s foremost peer-reviewed journals in the field of oncology.

Prof Lindy Durrant, Joint CEO of Scancell, said: “The publication of this paper on the science behind Moditope® in such a prestigious and widely read cancer journal is not only a great achievement for the research team at Scancell, it provides a ringing endorsement from the scientific community for this completely innovative approach to the treatment of cancer. This important paper lays out the foundation, rationale and experimental basis for the Moditope® platform and its potential to generate effective cancer vaccines.”

The lead product from the Moditope® platform, Modi-1, is progressing through pre-clinical development with first in man studies targeted in triple negative breast cancer and ovarian cancer patients.

Abstract

Citrullinated vimentin presented on MHC-II in tumor cells is a target for CD4+ T cell-mediated antitumor immunity

“Stressful conditions in the harsh tumor microenvironment induce autophagy in cancer cells as a mechanism to promote their survival. However, autophagy also causes post-translational modification of proteins which are recognized by the immune system. In particular, modified self-antigens can trigger CD4+ T cell responses that might be exploited to boost antitumor immune defenses. In this study, we investigated the ability of CD4 cells to target tumor-specific self-antigens modified by citrullination, which converts arginine residues in proteins to citrulline. Focusing on the intermediate filament protein vimentin, which is frequently citrullinated in cells during epithelial-to-mesenchymal transition of metastasizing epithelial tumors, we generated citrullinated vimentin peptides for immunization experiments in mice. Immunization with these peptides induced IFNγ- and granzyme B-secreting 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 60-90% of animals with no associated toxicity. This antitumor response was dependent on CD4 cells and not CD8+ T cells. 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 may offer especially attractive vaccine targets for cancer therapy.”

1. Victoria A Brentville, Rachael L Metheringham, Barbara Gunn, Peter Symonds, Ian Daniels, Mohamed Gijon, Katherine Cook, Wei
Xue, Lindy G Durrant; Published Online in Cancer Research, December 30, 2015, doi: 10.1158/0008-5472.CAN-15-1085

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About Scancell

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 and is being evaluated in a Phase 1/2 clinical trial. Data from the 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 Tlymphocyte 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.

About Cancer Research

Cancer Research is the most frequently cited cancer journal in the world. The journal publishes original studies, reviews, and opinion pieces offering significance and broad impact to a diverse audience spanning basic, preclinical, clinical, prevention, and epidemiologic research. Cancer Research seeks manuscripts that offer pathobiological and translational impact to inform the personal, clinical, and societal problems posed by cancer.