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Specific delivery of active biomolecules to treat lung cancer

Objective

Lung cancer is the second most common cancer and one of the most lethal types, with few effective treatment options. Potent biologics often fail clinically due to systemic toxicity, as they cannot be selectively delivered or activated at the tumour site. Immunotherapy exemplifies this: while established in cancer care, its use is often limited by severe side effects. This underscores the need for technologies enabling precise tumour targeting and local immune activation.
SafeDelivery will overcome this limitation by creating a programmable therapeutic platform that minimizes systemic toxicity by activating biologics exclusively at the tumour site. Our innovation lies in uniting two powerful technologies: our protein design FoldXpro software with AI-enhanced modules, to enable quantitative and specific protein masking (not functional util masking is removed), and Mycochassis, a cell-wall-deficient lung bacterial vector. FoldXpro will define quantitative rules for designing protein masking with predictable activity profiles. Mycochassis will be engineered to produce vesicles carrying RNA and proteins to selectively reprogram cancer cells, and to secrete or display enzymes that locally activate systemically administered masked biologics only within the tumour microenvironment. This represents the first (therapeutic) platform to integrate masking with in situ activation by a lung-tropic live vector. We will apply this strategy to chemokines, cytokines, and nanobodies active in tumours but limited by systemic toxicity. Designed molecules, will be validated in vitro, ex-vivo and in vivo using a lung cancer mouse model as proof of concept.
By integrating programmable protein masking with in situ bacterial delivery and activation, this work opens a new therapeutic paradigm for safe specific delivery of biologics. Beyond lung cancer, it will establish a generalizable framework for designing conditionally active proteins, enabling safer biologics for a range of diseases.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2025-ADG

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Host institution

FUNDACIO CENTRE DE REGULACIO GENOMICA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 3 323 826,00
Address
CARRER DOCTOR AIGUADER 88
08003 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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Total cost

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No data

Beneficiaries (1)