A Synthetic Microbial Therapy Rewires Antitumor Immunity Across Multiple Cancer Types

  • bioRxiv. 2026 Jul 22:2026.07.19.735925. doi: 10.64898/2026.07.19.735925.
Jugal K Das ,  Qing-Ming Qin ,  Shailbala Singh ,  Christina James Thomas ,  Shreyan Gupta ,  Ayan Chatterjee ,  Sunilgowda Sunnagatta Nagaraja ,  Fengguang Guo ,  Kaylee Delgado ,  Anil Kumar ,  Esther Ryu ,  Bennett Flannagan ,  Cansu Agca ,  Yuksel Agca ,  Noah Powell ,  Erin Barry ,  Melissa M Kahl-McDonagh ,  Sankar P Chaki ,  Andre Mendes Ribeiro Correa ,  Seyednami Niyakan ,  Song-I Han ,  James J Cai ,  Xiaoning Qian ,  Koichi S Kobayashi ,  Arum Han ,  Arul Jayaraman ,  Thomas A Ficht ,  Leslie Garry Adams ,  Robert C Alaniz ,  Cassian Yee ,  Jianxun Song ,  Paul de Figueiredo
PMID: 42539212 DOI: 10.64898/2026.07.19.735925
Abstract

Microbial immunotherapies show promise against Cancer, yet broad efficacy and mechanistic insight remain elusive. Here, we introduce SPIKE 1.0 (S1.0), a metabolically engineered bacterium that converts tryptophan into immunomodulatory hydroxyindoles via tryptophan monooxygenase to remodel the tumor microenvironment (TME). A single systemic dose of S1.0 elicited potent, durable antitumor responses across multiple murine models, including humanized mice, with minimal toxicity. S1.0 enhanced inflammatory signaling, activated innate and adaptive immunity, and promoted T cell persistence, memory, and resistance to exhaustion. It outperformed checkpoint inhibitors and synergized with chemotherapy. Multi-omics profiling revealed that S1.0 rewired amino acid metabolism in tumor-infiltrating immune cells and disrupted immunosuppressive networks. These results establish S1.0 as a scalable, cost-effective microbial immunotherapy with broad translational potential for solid Tumors.

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