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
Cliff Holloway, chief executive at Scancell Holdings Plc (LONSCLP), tells Proactive Investors they're raising up to £8mln through a placing and open offer – cash that will be used develop their three main drug candidates.
A placing and subscription at 12 pence a share will account for £6mln of the total.
The company also wants to include existing investors, so is planning a £2mln open offer of stock once the placing has been concluded.
Wed, 18 Apr 2018 12:18:00
In a separate announcement, the company said it was acquiring new technology from Nottingham University that will complement its current pipeline
Wed, 18 Apr 2018 13:15:00
The AIM-listed firm said its Moditope platform acts by stimulating the production of CD4+ T cells, which seek out and kill tumour cells that would otherwise be hidden from the immune system
Tue, 03 Apr 2018 05:40:00