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Oral Installation of Recombinant Methioninase-producing Escherichia coli into the Microbiome Inhibits Colon-cancer
Yutaro Kubota1,2,3, Qinghong Han1, Kazuyuki Hamada1,2,3
1AntiCancer Inc., San Diego, CA, U.S.A.
Background/Aim:
All cancer types so far tested are methionine-addicted. Targeting the methionine addiction of cancer with recombinant methioninase (rMETase) has shown great progress in vitro, in mouse models, and in the clinic. However, administration of rMETase requires multiple doses per day. In the present study, we determined if rMETase-producing Escherichia coli JM109 (E. coli JM109-rMETase) might be an effective anticancer agent when installed into the microbiome.
Materials And Methods:
E. coli JM109-rMETase was administered to a syngeneic model of MC38 colon cancer growing subcutaneously in C57BL/6 mice. JM109-rMETase was administered orally by gavage to the mice twice per day. Tumor size was measured with calipers.
Results:
The administration of E. coli JM109-rMETase twice a day significantly inhibited MC38 colon-cancer growth. E. coli JM109-rMETase was found in the stool of treated mice, indicating it had entered the microbiome.
Conclusion:
The present study indicates the potential of microbiome-based treatment of cancer targeting methionine addiction.
Insights
Engineered bacteria producing recombinant methioninase (rMETase) effectively inhibited colon cancer growth in mice. This microbiome-based approach targets cancer
Area of Science:
- Oncology
- Microbiome Research
- Biotechnology
Background:
- Methionine addiction is a common vulnerability across all tested cancer types.
- Recombinant methioninase (rMETase) shows promise in targeting this addiction but requires frequent dosing.
- Installing rMETase-producing bacteria into the microbiome offers a novel delivery strategy.
Purpose of the Study:
- To evaluate the efficacy of rMETase-producing Escherichia coli (E. coli JM109-rMETase) as an anticancer agent within the microbiome.
- To determine if oral administration of E. coli JM109-rMETase can inhibit tumor growth.
Main Methods:
- Administered E. coli JM109-rMETase orally to mice with subcutaneous MC38 colon cancer.
- Administered the bacteria twice daily via gavage.
- Monitored tumor growth by measuring size with calipers.
Main Results:
- Twice-daily oral administration of E. coli JM109-rMETase significantly inhibited MC38 colon cancer growth.
- The presence of E. coli JM109-rMETase in mouse stool confirmed its successful colonization of the microbiome.
Conclusions:
- Microbiome-based delivery of rMETase demonstrates potential for cancer treatment.
- This approach offers a new strategy for targeting methionine addiction in various cancers.
