Allogeneic B7-H3–Targeted CAR Vδ1T-cell Therapy in Advanced Solid Tumors: A Phase I Study

作者：Chang Liu, Jiarui Li, Dan Liu, Panpan Zhang, Miao Zhang, Ran Xue, J. Gong, Lian Liu, Min Tao, Siyuan Cheng, Ting Xu, Jiajia Yuan, Yanshuo Cao, Z. Wang, Yakun Wang, Jun Zhou, Ming Lu, Zhi Peng, Zhihao Lu, Jian Li, Xiaotian Zhang, T. Wang, Min Wang, Licui Jiang, H. Meng, Lin Yang, Changsong Qi, L. Shen · 发表于：Clinical Cancer Research · 年份：2026 · DOI：10.1158/1078-0432.ccr-25-4600 · 被引用次数：2 · 研究领域：CAR-T cell therapy research、Cancer Immunotherapy and Biomarkers、Monoclonal and Polyclonal Antibodies Research

PURPOSE: The aim of the study was to evaluate the safety, pharmacokinetics, and preliminary clinical activity of UTAA06, an "off-the-shelf" allogeneic B7-H3-targeted chimeric antigen receptor (CAR) Vδ1T-cell therapy, in patients with pretreated, advanced B7-H3-positive solid tumors. PATIENTS AND METHODS: In this first-in-human, phase I, dose-escalation study (NCT06372236), 10 patients with advanced solid tumors (including gastric, colorectal, hepatocellular, ovarian, and neuroendocrine cancers) were enrolled. Following lymphodepletion chemotherapy (cyclophosphamide and fludarabine), patients received UTAA06 infusion across three dose levels (5 × 108, 8 × 108, or 1 × 109 cells). The primary endpoint was safety. Secondary endpoints included pharmacokinetics and antitumor efficacy. RESULTS: UTAA06 demonstrated a manageable safety profile; no GVHD was observed, and cytokine release syndrome was limited to two transient grade 1 events. A single dose-limiting toxicity (grade 3 pneumonitis) was reported in one patient at the 5 × 108 cell dose level. Although UTAA06 demonstrated signals of biological activity, including transient reductions in serum tumor markers in 50% of patients, no objective response by RECIST v1.1 criteria was observed. Further analysis identified that the limited CAR T-cell persistence was likely driven by subclinical host-versus-graft rejection. CONCLUSIONS: This study provides clinical proof of concept for allogeneic B7-H3-targeted CAR-Vδ1T cells as a safe pl...