{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:12:04Z","timestamp":1768507924840,"version":"3.49.0"},"posted":{"date-parts":[[2023,8,28]]},"group-title":"Cancer Biology","reference-count":49,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,8,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>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 CEACAM6, a cell surface protein 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. Our results demonstrate that combining L DOS47 with anti-PD1 significantly increases the efficacy of anti-PD1 monotherapy, reducing tumor growth for up to 4 weeks.<\/jats:p>","DOI":"10.1101\/2023.08.28.555194","type":"posted-content","created":{"date-parts":[[2023,8,29]],"date-time":"2023-08-29T03:05:11Z","timestamp":1693278311000},"source":"Crossref","is-referenced-by-count":0,"title":["L-DOS47 enhances response to immunotherapy in pancreatic cancer tumor"],"prefix":"10.64898","author":[{"given":"Bruna Victorasso","family":"Jardim-Perassi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pietro","family":"Irrera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Abrahams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Veronica 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