Scancell is developing a pipeline of ImmunoBody® and Moditope® vaccines, primarily for the treatment of cancer
Scancell’s Immunobody® immunotherapy platform enhances the uptake and presentation of cancer antigens to harness the high avidity T cell responses that destroy tumours. The platform has been validated both in animals and in the clinic with SCIB1 but many opportunities also exist for the development of additional ImmunoBody® vaccines, both for cancer and chronic infectious diseases.
SCIB2 targets the lung cancer antigen NY-ESO-1. It has been developed to the point at which the product is fully defined and ready for further preclinical development as a potential immunotherapy for any tumour that expresses the NY-ESO-1 antigen such as lung, oesophageal, gastric, ovarian and bladder cancers.
ImmunoBody® vaccines for prostate, liver and colorectal cancer have also been further advanced.
Scancell’s Moditope® immunotherapy platform is based on exploiting the normal immune response to stressed cells, which is largely mediated by CD4+ T cells, and harnessing this mechanism to eradicate cancer cells. Scancell’s first target for Moditope® is vimentin – a major cytoskeletal protein found in mesenchymal cells. Many epithelial tumours switch from expression of cytokeratin to vimentin during metastasis in a process known as epithelial mesenchymal transition (EMT); this change in phenotype enables the cell to become mobile and metastasize to new locations in the body.
Scancell has now selected two modified vimentin peptides in which the arginine residues have been substituted by citrulline to form the basis of its first Moditope® development candidate, Modi-1. The inclusion of additional modified peptides from other Moditope® target proteins into Modi-1 is currently under review. Animal studies have shown that the two vimentin peptides stimulate potent anti-tumour responses and leads to significant improvements in survival, suggesting that the Modi-1 product could have outstanding potential as a novel immunotherapy. Immune response studies with cells isolated from cancer patients have confirmed that T cell responses were stimulated by both modified vimentin peptides.
Optimisation studies have identified the adjuvant, dose and administration route for testing Modi-1 in the First in Man study. In animal studies, an aggressive tumour cell line confirmed that the two vimentin peptides eradicate tumour cells in a therapeutic, and therefore clinically relevant, setting. Remarkably, these responses were evident when tumours had reached a late stage of development.
Moditope® vaccines have the potential to treat a wide variety of cancers. Scancell is currently further evaluating the initial indications for the first clinical trial with Modi-1 in terms of clinical need and market opportunity
Lindy G. Durrant, Rachael L. Metheringham and Victoria A. Brentville
Wei Xue, Victoria A. Brentville, Peter Symonds, Katherine W. Cook, Hideo Yagita, Rachael L. Metheringham and Lindy G. Durrant
Wei Xue, Rachael L. Metheringham, Victoria A. Brentville, Barbara Gunn, Peter Symonds, Hideo Yagita, Judith M. Ramage and Lindy G. Durrant
Victoria A. Brentville, Rachael L. Metheringham, Barbara Gunn, Peter Symonds, Ian Daniels, Mohamed Gijon, Katherine Cook, Wei Xue and Lindy G. Durrant
High avidity cytotoxic T lymphocytes can be selected into the memory pool but they are exquisitely sensitive to functional impairment (2012)
Victoria A. Brentville, Rachael L. Metheringham, Barbara Gunn and Lindy G. Durrant
Using monoclonal antibodies to stimulate antitumour cellular immunity (2011)
Lindy Durrant, Victoria Pudney and Ian Spendlove
Vaccines as early therapeutic interventions for cancer therapy: neutralising the immunosuppressive tumour environment and increasing T cell avidity may lead to improved responses (2010)
Lindy Durrant, Victoria Pudney, Ian Spendlove and Rachael Metheringham
DNA vaccination with T-cell epitopes encoded within Ab molecules induces high-avidity anti-tumor CD8 T cells (2009)
Victoria A. Pudney, Rachael L. Metheringham, Barbara Gunn, Ian Spendlove, Judith M. Ramage and Lindy G. Durrant
Antibodies designed as effective cancer vaccines (2009)
R.L. Metheringham, V.A. Pudney, B. Gunn, M. Towey, I. Spendlove and L.G. Durrant
Holloway says generating clinical data's a big focus for them in the near-term.
''Over the next two years we expect to see clinical readouts from two of our programmes - SCIB1 and Modi-1''.
''We'll be extending our pipeline particularly around Moditope with the Modi-3 programme, if we're successful with the grand challenge''.
''Then it's around looking at technical partnerships that will allow us to de-risk our developments''.
Thu, 15 Feb 2018 12:38:00
Dutch group ISA Pharmaceutical will incorporate its Amplivant technology into Modi-1, the first cancer treatment candidate being developed on the platform
Thu, 15 Feb 2018 15:00:00
Immuno-therapy SCIB1, which is expected to progress into Phase II clinical trials in the second-half of the year, was the focus of a peer-reviewed paper in OncoImmunology
Mon, 12 Feb 2018 11:50:00