Bruna Victorasso Jardim-Perassi, Pietro Irrera, Oluwaseyi E Oluwatola, Dominique Abrahams, Veronica C Estrella, Bryce Ordway, Samantha R Byrne, Andrew A Ojeda, Christopher J Whelan, Jongphil Kim, Matthew S Beatty, Sultan Damgaci-Erturk, Dario Livio Longo, Kim J Gaspar, Gabrielle M Siegers, Barbara A Centeno, Justin Y C Lau, Shari A Pilon-Thomas, Arig Ibrahim-Hashim, Robert J Gillies
Acidosis is an important immunosuppressive mechanism that leads to tumor growth. Therefore, we investigated the neutralization of tumor acidity to improve immunotherapy response. L-DOS47, a new targeted urease immunoconjugate designed to neutralize tumor acidity, has been well tolerated in phase I/IIa trials. L-DOS47 binds to CEACAM6, a cell-surface protein that is highly expressed in gastrointestinal cancers, allowing urease to cleave endogenous urea into two NH4+ and one CO2 , thereby raising local pH. To test the synergetic effect of neutralizing tumor acidity with immunotherapy, we developed a pancreatic orthotopic murine tumor model (KPC961) expressing human CEACAM6...
February 19, 2024: Biomedicines