A Synthetic Microbial Therapy Rewires Antitumor Immunity Across Multiple Cancer Types

Jugal Kishore 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 Ağca; Yüksel Ağca; Noah Powell; Erin Barry; Melissa M. Kahl-McDonagh; Sankar Prasad Chaki; André Mendes Ribeiro Corrêa; Seyednami Niyakan; Songlee Han; James Cai; Xiaoning Qian; Koichi S. Kobayashi; Arum Han; Arul Jayaraman; Thomas A. Ficht; L. Garry Adams; Robert Christopher Alaniz; Cassian Yee

doi:10.64898/2026.07.19.735925

ImmunologybioRxivJul 22, 2026

Preprint

A Synthetic Microbial Therapy Rewires Antitumor Immunity Across Multiple Cancer Types

Jugal Kishore Das iD, Qing‐Ming Qin iD, Shailbala Singh iD, Christina James Thomas, Shreyan Gupta iD, Ayan Chatterjee, Sunilgowda Sunnagatta Nagaraja iD, Fengguang Guo iD, Kaylee Delgado iD, Anil Kumar iD, Esther Ryu iD, Bennett Flannagan, Cansu Ağca, Yüksel Ağca iD, Noah Powell iD, Erin Barry, Melissa M. Kahl-McDonagh, Sankar Prasad Chaki iD, André Mendes Ribeiro Corrêa, Seyednami Niyakan iD, Songlee Han, James Cai iD, Xiaoning Qian iD, Koichi S. Kobayashi iD, Arum Han iD, , Paul de Figueiredo iD

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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.