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Separately, another DNA based anti-cancer vaccine combination treatment is showing early promise in ovarian cancer. An open-label prospective randomised study evaluated the safety and efficacy of ELENAGEN, a novel anti-cancer therapeutic DNA plasmid encoding p62/SQSTM1 protein, as an adjuvant to chemotherapy with gemcitabine in patients with advanced platinum-resistant ovarian cancer. The 2024 study found the treatment increased progression free survival from 2.8 months to 7.2 months compared to chemotherapy.
Dr Alexander Shneider, the primary author of the paper and founder of ELENAGEN’s creator company, CureLab Oncology, explained to MI how the science of DNA anti-cancer vaccines is overcoming its challenges.
“A car or an airplane didn’t become useful until engineers solved all the fundamental problems stumbling their performance. As far as at least one remained overlooked, the minimally functional car did not drive, and an airplane didn’t fly. I think a similar situation is taking place with anti-cancer DNA vaccines.”
In its early days, a DNA vaccine targeted only one particular antigen. So even if it was effective at the beginning, a tumour could omit producing the antigen and escape the immune response, Dr Shneider explained. However, today, due to the significantly reduced cost of deep sequencing, an era of neo-antigens came so that a DNA vaccine can be based on multiple mutated antigens specific for a specific tumour of a particular patient. Omitting multiple antigens is almost an unattainable task for a tumour. Also, scientists are finding tumour-associated antigens, which may be more challenging for a tumour to omit, he explained.
Another bottleneck for anti-cancer DNA vaccines was their relatively low immunogenicity. Thus, they were strong enough to treat a mouse but not a human. Slowly but surely, this bottleneck is also being resolved by applying the DNA vaccination regimen to enhance their effects; for example, adding adjuvants that do not target any specific antigen but increase an immune response overall.
“Finally, the main remaining bottleneck is so-called ‘cold tumours’, constituting the majority of many cancers. These are the tumours that are impenetrable to immune cells, so the lymphocytes that could eliminate cancer cells do not get into the tumour. Hopefully, our product, ELENAGEN, will solve this problem by changing the intra-tumoural structure and turning ‘cold’ tumours into ‘hot’ ones. Based on our published animal data, it seems like ELENAGEN changes the extracellular matrix, the molecular ‘chains’ connecting cells within a tumour into a particular architecture, and opens the doors for immune cells to enter the tumour.”.
