ENO3PEP: DNA vaccine for the treatment of pancreatic ductal adenocarcinoma
We identified alpha-enolase (ENO1) as a molecule aberrantly expressed by pancreatic cancer cells and recognized by antibodies present in pancreatic ductal adenocarcinoma (PDA) patients but not in healthy or autoimmune controls. Therefore, we developed a first generation DNA vaccine able to delay PDA growth in pre-clinical mouse models. Based on this results, we developed a second generation vaccine.
The first generation DNA vaccine expressing the whole protein has proven to be efficient in prolonging the survival of animals by triggering an integrated immune response. To further enhance the efficacy of the vaccine-induced anti-tumor response, we decided to exploit those ENO1 sequences that may be more efficient in activating T lymphocytes defined as immunogenic. This had the purpose of better focusing the lymphocyte response and avoiding unnecessary “competition or distraction” that would dampen the final anti-tumor response. To this, we assessed the ability of a library of long peptides to induce the proliferation and the cytokine secretion from T cells obtained both from healthy donors and PDA patients. Six sequences were identified as greater performers compared to the full-length ENO1. Therefore, the proposed solution consists of a DNA vaccine containing only those six sequences of ENO1 protein that was revealed to be more efficient in activating T lymphocytes.
- Treatment of the pancreatic ductal adenocarcinoma;
- Neoadjuvant therapy, administered before surgery;
- Adjuvant therapy, administered after resection.
- Easy to produce;
- It doesn’t require a stringent cold chain;
- It doesn’t require particular technical skills in administration;
- It induce the activation of specific cytotoxic T lymphocytes.