{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T05:46:34Z","timestamp":1794375994076,"version":"4.9.0"},"reference-count":42,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"21","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,7,20]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>The clinical efficacies of third- or later-line therapies for metastatic colorectal cancer (CRC) are extremely limited. The purpose of this study was to evaluate the safety and efficacy of a chimeric antigen receptor T (CAR T) cell targeting guanylyl cyclase 2C (GUCY2C) that was steadily expressed in all stages of CRC in a phase I study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>\n                      This was an open-label, single-center, phase I study, consisting of a 3 + 3 pattern dose-escalation phase and a dose-expansion investigation. Tumor tissues were histologically confirmed positive for GUCY2C expression. Four dose levels were tested in the dose-escalation phase, including 3 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      (DL1), 6 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      (DL2), 12 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      (DL3), and 20 \u00d7 10\n                      <jats:sup>8<\/jats:sup>\n                      (DL4) CAR T cells. The primary end points were safety and tolerability within 28 days after the first infusion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>In the dose-escalation phase, dose-limiting toxicity was not observed. DL3 was chosen for dose-expansion study. A total of 20 patients with metastatic CRC were infused with GUCY2C CAR T after lymphodepletion, and only one patient (5.0%) showed grade 3 cytokine release syndrome and neurotoxicity. Grade 3 diarrhea occurred in 11 patients (55.0%). Of 19 evaluable patients, the objective response rate (ORR) was 26.3%, with all responding patients in DL3 and DL4 groups. Of 10 patients in the DL3 group, the ORR was 40.0% and the median progression-free survival time (mPFS) was 7.0 months. Among patients showing medium-to-high GUCY2C expression in the DL3 group, the ORR achieved 50.0% and the mPFS was 9.0 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>GUCY2C CAR T showed acceptable safety profile and high response rate in patients with third- or later-line CRC, and the clinical efficacy was associated with CAR T dose level.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-01090","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T19:59:20Z","timestamp":1780603160000},"page":"2006-2016","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":8,"title":["Guanylyl Cyclase 2C\u2013Targeted Chimeric Antigen Receptor T-Cell Therapy in Patients With Metastatic Colorectal 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