NIH grant: Bioengineered Networking Microbes for Targeted Colon Cancer Therapy (1R21CA309636-01A1)

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NIH grant 1R21CA309636-01A1: Bioengineered Networking Microbes for Targeted Colon Cancer Therapy
Institute: {'code': 'CA', 'abbreviation': 'NCI', 'name': 'National Cancer Institute', 'admin_org_id': '12500008', 'admin_funding_url': ''}. PI: Wei  Kong. Award: $403686.
Start: 2026-07-16T00:00:00.
Project Summary
Colon cancer remains a critical global health challenge, intensified by the rising incidence of early-onset disease
and the persistence of immunologically cold and metastatic tumors that evade conventional therapies. To
address these unmet needs, this project develops bioengineered networking microbes, a coordinated system of
genetically modified bacteria designed to selectively target tumors and reprogram the host immune environment.
We have developed genetically modified Salmonella (GMS) engineered to deliver TRAIL and capable of homing
to tumor sites, colonizing the tumor microenvironment, and initiating localized inflammatory responses that
increase tumor immunogenicity. In multiple preclinical mouse models, TRAIL-expressing GMS induce potent
tumor cell apoptosis, amplify immune activation through the release of tumor-associated antigens, inhibit tumor
growth, prolong survival, and reduce metastatic spread. Complementing this oncolytic platform, we also engineer
beneficial gut bacteria to restore microbial balance, reduce inflammation, and modulate metabolites implicated
in colon cancer progression. By integrating tumor-targeting bacteria with microbiome-restorative strains, we
propose a synergistic therapeutic approach in which engineered microbes communicate and cooperate to
enhance tumor targeting, strengthen anti-tumor immunity, and improve overall treatment efficacy. Animal models
are essential for proposed research to evaluate the safety, biodistribution, and therapeutic efficacy of the
engineered microbial consortium within the complex tumor and immune microenvironment. They also enable
investigation of host-microbiome-tumor interactions and cooperative microbial behaviors that cannot be
adequately replicated in vitro. If successful, this project will establish a transformative paradigm in colon cancer
therapy-leveraging networked, multifunctional microbes as both precise local activators of anti-tumor immunity
and systemic modulators of gut health to achieve durable and broadly applicable therapeutic responses.

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