Scientists at the Centre for Cancer Immunology alongside Cancer Research UK and Touchlight Genetics, a London based biotechnology company, have announced a new clinical development partnership to progress a therapeutic DNA vaccine, TGL-100, into an early phase clinical trial targeting head and neck squamous cell carcinoma (HNSCC).
HNSCC is the UK’s eighth most common cancer, but treatment options are limited and around 4,000 of those affected in the UK die each year. Whilst existing immunotherapies have a huge impact for a small number of cancer patients, it is hoped that targeted cancer vaccines could extend this benefit to many more people.
DNA cancer vaccines encode antigens from cancer cells that prime the immune system, waking up immune cells that can tackle cancer. These therapies have shown significant promise in clinical studies. However, to date, they have been based on circular plasmid DNA, which means their use is limited by slow and expensive manufacturing.*
The newly designed DNA vaccine combines potent cancer antigens with Touchlight Genetics’ novel DNA vector – Doggybone DNA™ (dbDNA). Unlike plasmid DNA vectors, dbDNA is a double-stranded, linear, covalently closed molecule, which is an optimal vector for advanced therapies.**
TGL-100 encodes two antigens overexpressed in HNSCC to induce an antigen-specific anti-tumour immune response in the body. This preclinical development was led by Dr Natalia Savelyeva at the Centre for Cancer Immunology at the University of Southampton in partnership with Dr Kue Peng Lim at Cancer Research Malaysia, and the clinical trial will be led by Professor Christian Ottensmeier.
Jonny Ohlson, CEO of Touchlight Genetics said: “TGL-100 emerged from a collaboration with the brilliant Christian Ottensmeier and his talented team at the University of Southampton. Partnering with Cancer Research UK will provide the regulatory know-how, clinical expertise and operational capability to help translate this potentially transformative class of personalised therapies into patient benefit.”
Under the terms of the agreement, Cancer Research UK’s Centre for Drug Development will sponsor and manage the Phase I/II trial to test TGL-100 in HNSCC patients with recurrent metastatic disease.***
Dr Nigel Blackburn, Cancer Research UK’s Director of Drug Development, said: “We’re delighted to be working with Touchlight Genetics and the University of Southampton at the forefront of oncology innovation. Through our collaboration we’ve been able to accelerate the development of this promising experimental vaccine and hope to see benefit for patients with HNSCC, a cancer that is hard to treat.”
The proposed clinical trial will test a new combination strategy of vaccination alongside a currently available PD-1 checkpoint inhibitor. This combination could markedly improve a HNSCC patient’s response to the checkpoint inhibitor and could lead to patients living longer.
Professor Christian Ottensmeier, Chief Clinical Investigator at the University of Southampton, said: “We hope this new DNA cancer vaccine will wake up immune cells already present at the tumour site and train new T cells to travel to the cancer tissue so they can fight the cancer.
“We expect that this trial will deliver fundamental insights into how we can use cancer vaccines in the most optimal way so we can boost survival for people with head and neck cancer.”
* Touchlight’s novel cell-free manufacturing method doesn’t require fermentation, one of the challenges of plasmid DNA production, making dbDNA production significantly faster and more scalable. This, in turn, enables a simpler route to commercialisation and the potential for rapid, fully personalised vaccination strategies. The dbDNA vector also eliminates bacterial sequences and antibiotic resistance genes, conferring a safety advantage.
** Touchlight has developed, patented, and scaled the fully enzymatic means of large-scale DNA amplification. It can produce multi-gram batches in a 5-day, benchtop process in a facility with minimal requirements. Doggybone is manufactured at Touchlight Genetics’ GMP facility in Hampton, UK. The structure eliminates backbone sequences for improved safety and dosing. Cancer Research UK’s Centre for Drug Development and Touchlight have received advice from the MHRA regarding approval for the Doggybone construct.
*** Most pipeline agents target HPV-driven HNSCC. This study will recruit HNSCC patients identified by early preclinical studies in collaboration with the University of Southampton and Touchlight Genetics. The DNA vaccine may offer a strategy to boost immune response in non-HPV driven HNSCC. Upon trial completion, Touchlight Genetics retains the option to undertake further clinical development and commercialisation of the vaccination strategy. If Touchlight elects not to exercise its option, Cancer Research UK will have the rights to take the programme forward in all cancer indications.