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Live biotherapeutics to potentiate cancer immunotherapy


Engineered bacteria make tumours more accessible to therapeutics

Despite initial promise, many immunotherapeutic approaches are associated with adverse immune-related effects. An immunosuppressive and hostile tumour microenvironment is believed to impede the success of immunotherapy by limiting oxygen supply and delivery of the therapeutic. Funded by the European Research Council, the LiveBioThx project proposes to develop engineered bacteria as a delivery vehicle of enzymes to the tumour microenvironment. The idea is to reduce tumour stiffness and improve perfusion through tumour remodelling. The LiveBioThx live biotherapeutic product is expected to improve the potency and clinical outcome of immunotherapies such as checkpoint inhibitors.


Immunotherapy, including immune checkpoint inhibitors (ICIs), has revolutionized the treatment of multiple cancers. Anti-tumor responses are often durable but overall only a subset of patients receiving ICIs has exhibited sustained tumor shrinkage, whereas a substantial fraction receiving these therapies develops immune-related adverse events. The absence of dramatic responses is attributed to several factors, including abnormalities in the tumor microenvironment (TME). Specifically, many tumors such as subsets of colorectal, breast and pancreatic cancer, become stiff as they grow. Tumor stiffening causes compression of intratumor blood vessels, impairing blood flow/perfusion and oxygen supply. Hypoperfusion reduces ICIs delivery to the tumor and hypoxia induces immunosuppression, compromising immunotherapy. To restore these abnormalities, a novel therapeutic strategy to normalize tumor stiffness prior to ICIs has been tested in preclinical studies and in the clinic. This strategy repurposes clinically approved drugs to target the factors contributing to tumor stiffening, leading to a new class of therapeutics, known as mechanotherapeutics. However, drug-repurposing poses certain limitations as adding a new drug to the treatment regimen of patients with cancer is not feasible in many cases. As an alternative to these approaches, we propose here to test the ability of engineered live biotherapeutics in the form of programmable bacteria that offer unique advantages for delivering enzymes to normalize the TME. Even a small fraction of bacterial dose reaching the tumor is sufficient to colonize it and allow therapeutic concentrations of tumor-remodeling enzymes to be maintained for a long period of time. We propose to evaluate the ability of a novel live biotherapeutic product to improve perfusion and potentiate ICIs in preclinical tumor models of colorectal and breast tumors. This bacterial product has great potential for commercialization, and a plan is proposed.



ERC-POC - Proof of Concept Grant


€ 150 000,00
Avenue panepistimiou 2109 aglantzi
1678 Nicosia


Κύπρος Κύπρος Κύπρος
Higher or Secondary Education Establishments