Stimulating the production of killer CD4+ T cells that destroy tumours without toxicity
Moditope® represents a completely new class of potent and selective immunotherapy agents which could have a profound effect on the way that cancer immunotherapies are developed. It acts by stimulating the production of CD4+ T cells using citrullinated tumour-associated peptide epitopes which overcome self-tolerance and destroy tumour cells. The technology overcomes the immune suppression induced by tumours themselves without the need for checkpoint blockade inhibitors, thereby allowing activated T cells to seek out and kill tumour cells that would otherwise be hidden from the immune system.
It has the potential to be used to develop multiple immunotherapeutic agents for a wide range of different cancers. A broad patent has been filed to protect this platform covering the use of multiple tumour-associated modified epitopes for the treatment of cancer.
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
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