Scholarlink

<p>Engineered attenuated <i>Salmonella typhimurium</i> has been explored as a tumor-targeting platform for localized therapeutic delivery. Here, we developed a strain capable of secreting the N-methyl-D-aspartate receptor (NMDAR) antagonist conantokin G (Con G) via the flagellar type III secretion system (T3SS). The engineered bacteria preferentially accumulated in tumor tissues and induced robust colorectal cancer cell death characterized by membrane disruption, leading to significant tumor suppression in vitro and in vivo with minimal systemic toxicity. Bulk RNA-seq analysis confirmed induction of immunogenic cell death pathways and concurrent suppression of Treg-associated gene expression. <i>Salmonella</i> colonization was associated with increased tumor PD-L1 expression, likely driven by infection-induced inflammatory signaling, which provided a rationale for combination with α–PD-L1 therapy. Combination treatment enhanced tumor regression, prolonged survival, and achieved complete tumor clearance in a subset of mice. Analysis of 106 clinical colorectal cancer specimens further demonstrated that high expression of NR2B, a subunit of NMDAR, is associated with advanced disease stage and poor prognosis. Together, these findings establish NR2B as a clinically relevant therapeutic target and highlight engineered bacterial delivery of Con G as a strategy to sensitize colorectal cancer to immune checkpoint blockade.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Engineered Salmonella delivering the NMDAR antagonist conantokin G synergizes with PD-L1 blockade to enhance colorectal cancer regression

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月15日

查看全文
  • Solbi Kim,
  • Sora Kang,
  • Eunji Kim,
  • Minju Han,
  • Minchan Jeong,
  • Jin-Man Kim,
  • Heung Jin Jeon,
  • Hyo-Jin Lee

摘要

Engineered attenuated Salmonella typhimurium has been explored as a tumor-targeting platform for localized therapeutic delivery. Here, we developed a strain capable of secreting the N-methyl-D-aspartate receptor (NMDAR) antagonist conantokin G (Con G) via the flagellar type III secretion system (T3SS). The engineered bacteria preferentially accumulated in tumor tissues and induced robust colorectal cancer cell death characterized by membrane disruption, leading to significant tumor suppression in vitro and in vivo with minimal systemic toxicity. Bulk RNA-seq analysis confirmed induction of immunogenic cell death pathways and concurrent suppression of Treg-associated gene expression. Salmonella colonization was associated with increased tumor PD-L1 expression, likely driven by infection-induced inflammatory signaling, which provided a rationale for combination with α–PD-L1 therapy. Combination treatment enhanced tumor regression, prolonged survival, and achieved complete tumor clearance in a subset of mice. Analysis of 106 clinical colorectal cancer specimens further demonstrated that high expression of NR2B, a subunit of NMDAR, is associated with advanced disease stage and poor prognosis. Together, these findings establish NR2B as a clinically relevant therapeutic target and highlight engineered bacterial delivery of Con G as a strategy to sensitize colorectal cancer to immune checkpoint blockade.