Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity

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Paper Summary

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Bacteria Delivering STING Agonists: A New Approach to Cancer Immunotherapy

This study demonstrates that engineered E. coli Nissle (SYNB1891) can be used to deliver a STING agonist (CDA) directly to tumor-infiltrating APCs, resulting in potent anti-tumor immunity in murine models. SYNB1891 activates STING signaling, triggers proinflammatory cytokine production, and generates immunological memory, resulting in durable tumor rejection in a proportion of treated mice.

Possible Conflicts of Interest

All authors are or were employees of Synlogic, Inc., which developed SYNB1891. This represents a potential conflict of interest.

Identified Weaknesses

Translatability to Human Efficacy

While the study demonstrates promising results in preclinical models, its translatability to human efficacy remains to be determined, as previous bacterial-based therapies have faced challenges in clinical trials. The study emphasizes the need for clinical testing (NCT04167137) to assess safety, tolerability, and efficacy in humans.

Potential Detrimental Effects on T Cells

The study acknowledges that targeting STING in T cells could be detrimental. Further investigation is needed to understand the potential impact of SYNB1891 on T cell responses and long-term antitumor immunity.

Limited Human In Vivo Data

While tested on multiple human STING alleles in vitro, the in vivo studies primarily focus on murine models, leaving open the question of whether the observed efficacy translates consistently to diverse human patient populations with varying STING genotypes and tumor microenvironments.

Limited Delivery Method

The reliance on intratumoral injection limits the applicability of SYNB1891 to easily accessible tumors, excluding many visceral or deep-seated lesions. While future studies might explore alternative delivery methods, the current approach restricts the treatment's scope.

Rating Explanation

The study presents a novel approach to cancer immunotherapy using engineered bacteria for localized STING activation. It demonstrates promising preclinical efficacy and addresses key translational challenges, like safety, biocontainment, and manufacturability, achieving a balance between innovation and clinical feasibility. The reliance on intratumoral injection, potential T cell impact, and limited human in vivo data constitute moderate limitations.

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Topic Hierarchy

Domain:

Life Sciences

Field:

Biochemistry, Genetics and Molecular Biology

Subfield:

Biotechnology

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Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity

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