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Tumor acidosis targeted delivery of immunotherapy by Marker-Agnostic TumoR-Anchoring Chimeras

Project description

New tech for acidic tumour-targeted immunotherapy delivery

Cancer immunotherapy uses the immune system to target tumours more precisely than traditional treatments. However, it still faces challenges with certain tumours and side effects. The ERC-funded MATRACs project aims to explore an innovative approach using Marker-Agnostic TumoR-Anchoring Chimaera (MATRAC) technology to use the acidic microenvironment of solid tumours for targeted delivery of immune-modulating therapies. MATRACs are designed fusion proteins that connect a therapeutic agent with a pH-responsive mechanism, activating treatment in acidic tumour sites while minimising off-target effects. Early studies indicate that MATRACs enhance tumour localisation, demonstrate pH-selective binding, and stimulate immune responses. This research is expected to improve their efficacy and safety through evaluations of pharmacokinetics, immunogenicity, and toxicity.

Objective

Cancer immunotherapy represents a groundbreaking advancement in oncology, leveraging the immune system to combat malignancies with enhanced specificity and reduced systemic toxicity compared to traditional therapies. However, despite significant progress, current immunotherapies face limitations, particularly in targCancer immunotherapy represents a groundbreaking advancement in oncology, leveraging the immune system to combat malignancies with enhanced specificity and reduced systemic toxicity compared to traditional therapies. However, despite significant progress, current immunotherapies face limitations, particularly in targeting tumors without identifiable antigenic signatures and avoiding immune-related adverse events. In my ERC project I will explore an innovative approach utilizing Marker-Agnostic TumoR-Anchoring Chimera (MATRAC) technology, designed to harness the universal acidic microenvironment of solid tumors for targeted delivery of immune-modulating therapies. MATRACs are engineered recombinant fusion proteins that combine a therapeutic payload with a pH-responsive anchoring mechanism, ensuring selective activation in acidic tumor sites while minimizing off-target effects. Preliminary studies demonstrate MATRACs' enhanced tumor localization, pH-selective membrane binding, and potent immune-stimulating effects, laying the groundwork for their development as a versatile platform for innate immune-mediated cytotoxicity, cytokine therapy, and T-cell engagement in various cancer models. This research aims to optimize MATRACs' therapeutic efficacy and safety, with comprehensive preclinical evaluations including pharmacokinetics, immunogenicity, and toxicity assessments. By addressing critical gaps in current cancer immunotherapy, MATRAC technology holds the potential to expand treatment options for a broader range of patients, particularly those with antigenically challenging tumors, while improving the precision and effectiveness of immune-based therapies.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2024-ADG

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Host institution

UNIVERSITEIT GENT
Net EU contribution
€ 2 500 000,00
Address
SINT PIETERSNIEUWSTRAAT 25
9000 Gent
Belgium
Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Beneficiaries (1)