Combining SCIB2 with CTLA-4 blockade enhances tumour destruction and extends survival times
Scancell Holdings plc (‘Scancell’ or the ‘Company’), the developer of novel immunotherapies for the treatment of cancer, is pleased to announce new data demonstrating that animals treated with a combination of SCIB2, Scancell’s ImmunoBody® vaccine in development for the treatment of lung, oesophageal, prostate and other epithelial cancers, and checkpoint inhibition (blockade of the CTLA-4 immune checkpoint pathway), showed enhanced tumour destruction and significantly longer survival times than when either treatment was used alone.
The data confirming the therapeutic effect of SCIB2 with this second checkpoint pathway follows our previous announcement on 12 August 2014 of SCIB1’s synergy with PD-1 blockade in animal models.
In earlier pre-clinical studies, we have shown that administration of SCIB2 alone induced potent tumour-specific T cell responses associated with increased T cell infiltration into the tumour and enhanced proliferation of T cells within the tumour resulting in tumour rejection and long term survival. In our new study where higher doses of tumour cells were used, the combination of CTLA-4 blockade with SCIB2 vaccination resulted in a significant survival advantage over the individual treatments. Although patients with a relatively low tumour burden may benefit from SCIB2 alone, these results highlight the potential benefits of combining SCIB2 with CTLA-4 blockade, such as ipilimumab, for the treatment of patients with advanced disease.
SCIB2 is a DNA plasmid targeting the cancer antigen NY-ESO-1. It induces high avidity CD8 and CD4 responses in pre-clinical models and unlike SCIB1 which is only suitable for patients with the HLA-A2 subtype (around 50% of patients), SCIB2 has been engineered to be effective in over 90% of immune subtypes, further enhancing the market potential and reducing the need for HLA screening prior to treatment. All future ImmunoBody® vaccines will now be engineered to this new standard.
Checkpoint inhibitors can enable the host immune system to recognise, attack and destroy cancer cells. However, checkpoint inhibitors will not work on their own if the patient fails to mount an adequate immune response to the tumour. Taking the brake off immunosuppressive T cells with either CTLA-4 or PD-1 blockade, whilst simultaneously pressing the accelerator with active immunotherapies such as SCIB1 or SCIB2, is increasingly regarded as offering potential for overwhelming the disease and increasing efficacy.
Prof Lindy Durrant, Joint CEO of Scancell and Professor of Cancer Immunotherapy at Nottingham University, commented: “The rationale for combining Scancell’s ImmunoBody® vaccines with checkpoint inhibitors is gathering momentum. Whilst we believe that SCIB2, like SCIB1, will provide effective stand-alone treatment in the adjuvant setting, these data further support the hypothesis that some patients with more bulky disease will benefit from a combination of SCIB2 with CTLA-4 blockade.”
For Further Information:
Dr Richard Goodfellow, Joint CEO
Professor Lindy Durrant, Joint CEO
|Scancell Holdings Plc
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Robert Naylor/Maisie Atkinson
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|Mo Noonan/Simon Conway
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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 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.
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 and checkpoint inhibition (blockade of the PD-1 immune checkpoint pathway) has 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.