CELL INTELLIGENCE · 肿瘤细胞治疗研究

Chimeric antigen receptor (CAR) T cell therapy for solid tumors remains challenging. This phase 1, open-label, dose-escalation and expansion study (ClinicalTrials. gov registration: NCT05396300 ) evaluated the safety and efficacy of PC13, a hypoxia-responsive, carcinoembryonic antigen (CEA)-targeted CAR T cell therapy, in persons with CEA-positive solid tumors. The primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics and pharmacodynamics. A total of 43 heavily pretreated participants (46. 5% with 4 prior lines) were assigned to receive PC13 through intraperitoneal (I. P. , n = 17) or intravenous (I. V.

, n = 26) infusion on the basis of predominant metastatic sites. Grade 3 diarrhea occurred in 20. 9% of participants and 76. 7% experienced grade 1 or 2 cytokine release syndrome. Disease control rates were 82. 4% in the I. P. group and 68. 0% in the I. V. group, with objective response rates (ORRs) of 23. 5% and 8. 0%, respectively.

In post hoc analyses, ORRs reached 57. 1% (4/7) in the I. P. group with peritoneal metastases and 40. 0% (2/5) in the I. V. group without liver metastases, both among participants with CEA immunohistochemistry expression 90%. The predefined safety endpoint was met. PC13 demonstrated manageable toxicity and promising efficacy, supporting further investigations.