Non-Armored GCC-targeting CAR-T cell therapy demonstrates significant efficacy in patients with advanced colorectal cancer.

Authors

Qianyu Zhang, Lin Lin, Wei Wang, Ling He, Lin Wang, Wenjuan Li, Qiujun Zhang, Dandan Hu, Sheng Wu, Wenyu Li, Shoubing Zhou, Wei Jin, JIng Pan, Yabei Liu, Yueyin Pan, Xiaohu Fan, Hu Liu

Published in

Clinical cancer research : an official journal of the American Association for Cancer Research. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

This phase 1 clinical trial aims to evaluate the safety, expansion kinetics, and preliminary efficacy of non-armored, nanobody-derived GCC-targeted CAR-T cells in patients with heavily pretreated, metastatic colorectal cancer.
In this single-arm, open-label, phase 1 clinical trial, twenty-four patients who received at least two prior lines of treatment received GCC-targeted CAR-T cells across four dose levels: 0.5×105, 1×106, 2×106,and 3×106 CAR-T cells/kg. The primary endpoint was safety; secondary endpoints included antitumor activity and pharmacokinetics.
All patients experienced grade 3 or higher hematologic toxicity, and 75% developed cytokine release syndrome, both of which were generally manageable. Two treatment-related deaths occurred, one due to immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome and one due to intestinal fistula following rapid tumor regression in a lesion adherent to the intestinal wall. The overall response rate (ORR) and disease control rate (DCR) reached 33% and 63%, respectively. Eight patients achieved a partial response (PR) as their best response, seven maintained stable disease (SD), and five had progressive disease (PD). Median progression-free survival (mPFS) was 57 days and median overall survival (mOS) was 190 days. Higher in vivo CAR-T expansion was associated with better disease control. Proof-of-concept activity was demonstrated, although response durability was limited and toxicity remains challenging.
GCC-targeted CAR-T cells demonstrated encouraging antitumor activity in heavily pretreated CRC patients, with the initial data supporting GCC as a clinically actionable target. Further development will require dose selection, patient eligibility, and toxicity management optimization to improve the therapeutic profile.

PMID:
42467218
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.

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