Advancements in Pancreatic Cancer Immunotherapy: The Efficacy and Safety of TYG100 Vaccine in Primates

A clinical approach involving immunization against gastrin, a hormone linked to pancreatic cancer progression, has been explored. Previous trials with a DT-conjugated gastrin peptide vaccine (G17DT) demonstrated an extension in median survival for patients not suitable for chemotherapy, with a significant benefit observed in immunological responders. However, the survival advantage was limited to 70% of participants, indicating a need for a more effective vaccine to increase the immune response rate. Additionally, injection site reactions were a concern that restricted the number of doses some patients could receive.

To address these issues, a new recombinant vaccine, TYG100, has been developed using the S-TIR platform. This vaccine is designed to target the gastrin immunogen to antigen-presenting cells that express CD32 while also activating plasmacytoid dendritic cells due to its intrinsic adjuvant properties. TYG100, when applied to little gastrin (G17), has been shown to elicit minimal injection site reactions and robust gastrin-neutralizing responses.

In a study involving cynomolgus monkeys, TYG100 was administered in three doses and resulted in a rapid and strong immune response with no signs of adverse reactions. The antibodies generated were effective against both forms of human G17. The results suggest a substantial increase in the magnitude of the immune response compared to the earlier G17DT immunogen, and the antibodies produced were capable of neutralizing both forms of the gastrin hormone.

The development of TYG100 represents a significant advancement in the field of pancreatic cancer vaccines, with the potential to significantly increase the proportion of patients responding to immunotherapy and thereby improve survival outcomes. This novel vaccine construct could offer a considerable advancement in gastrin-targeted therapy for pancreatic cancer.