A tumor-targeted arginine depletion and toxic analog combination therapy system based on step-by-step oral administration of homologous engineered bacteria and phage cascade amplification

By using a cascade amplification system of the same engineered bacteria, bacteriophages were used to achieve local arginine depletion in tumors and precise delivery of canavalialine, solving the problems of drug resistance and toxicity in arginine deprivation therapy and achieving high efficiency and safety in tumor treatment.

CN122376789APending Publication Date: 2026-07-14GUANGZHOU XINGLIN NO 1 BIOTECHNOLOGY CO LTD
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Patent Information

Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
GUANGZHOU XINGLIN NO 1 BIOTECHNOLOGY CO LTD
Filing Date
2026-05-10
Publication Date
2026-07-14

AI Technical Summary

Technical Problem

In the prior art, arginine deprivation therapy is effective for arginine auxotrophic tumors lacking arginine succinate synthase 1, but it is prone to drug resistance. Furthermore, canavalialine is generally toxic to living systems, making it difficult to safely produce and deliver in a living factory.

Method used

Using a cascade amplification system of the same engineered bacteria, and through a stepwise strategy of colonizing bacteria and effector bacteria, bacteriophages are used to achieve precise delivery of arginine depletion and toxic canavanine in the tumor local area, separating production and delivery in time and space, and combining neutralizing antibodies to ensure safety.

Benefits of technology

This approach achieves temporal and spatial separation of arginine depletion at the tumor site and canavonicine delivery, avoiding toxicity to the factory bacteria, improving therapeutic efficacy and reversing drug resistance, while ensuring systemic safety.

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Abstract

This invention discloses a precision combined tumor treatment system that uses the same engineered bacteria as a substrate, delivered orally in two stages to achieve a spatiotemporally controlled combined treatment of "starvation therapy" and "toxic amino acid analogue therapy." The first stage involves orally administered colonizing bacteria, which do not contain bacteriophages, that colonize the tumor's hypoxic microenvironment and initially express arginine-metabolizing enzymes. Five to seven days later, the second stage involves orally administered effector bacteria carrying a genetically engineered lysogenic bacteriophage. This bacteriophage is designed to initiate lysis and proliferation only under the logical "AND" gate regulation of multiple signals specific to tumors, such as hypoxia, high lactate, and low pH. Because the colonizing and effector bacteria are from the same substrate, the bacteriophage can efficiently cross-infect the already colonized bacteria without any host recognition modification. Through a cascade amplification cycle of "infection-replication-lysis-reinfection," it instantaneously releases high concentrations of arginine-metabolizing enzymes, completely depleting the tumor's local arginine reserves. Simultaneously, neutralizing antibodies are used to remove any enzyme proteins that leak into the bloodstream, ensuring systemic safety. After confirming arginine depletion, a low dose of canavaliain is administered orally. Starved tumor cells, in their indiscriminate feeding, inadvertently ingest large amounts of this toxic analogue, achieving precise targeting and significantly sensitizing radiotherapy and chemotherapy or reversing drug resistance. This invention simplifies the production process and eliminates phage host recognition barriers through a dual-purpose design of the same substrate bacteria, maximizing cascade amplification efficiency.
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