Project: Development of CXCR4 targeting-nanosystem-probes for molecular imaging of cancer cells and tumor microenvironment.
| Acronym | NAN-4-TUM (Reference Number: EURONANOMED2019-044) |
| Duration | 01/01/2020 - 31/12/2022 |
| Project Topic | Biomarkers of sensitivity and response to immune inhibitory checkpoints (ICI) are urgently needed. CXCR4 is overexpressed in more than 20 human cancers contributing to their metastatic dissemination/growth progression. Non-invasive monitoring and quantification of CXCR4 expression in tumors allows 1.CXCR4-expressing tumor diagnosis/follow up and 2.TME characterization. A new family of CXCR4 peptide antagonists was developed (PCT/IB2011/EP2528936B1/US2013/0079292A1) with Peptide R being the lead compound. Peptide R decorated pegylated liposomes improved efficacy and stability of the unconjugated form. Excellent self-assembling supramolecular dendrimer nanosystem-SSDN was recently developed for PET imaging of tumor with significantly higher efficacy in terms of sensitivity, specificity and accuracy. Aim of the project is to develop CXCR4 targeting-nanosystem-imaging probes toward Tumor and TME-CXCR4 expressing with a diagnostic and predictive value. Objectives: • To construct CXCR4 targeting-nanosystem with: Pegylated liposomes-CXCR4 antagonists decorated or SSDNs-CXCR4 antagonists. Characterization for size, morphology and stability as well as receptor binding and functional CXCR4 inhibition in vitro and in vivo in models of solid tumors and PDX (colon, gastric, renal and NETs). • To develop CXCR4 targeting-nanosystem-[68Ga] based radiotracer. Evaluation of targeting specificity, internalization, biodistribution and toxicity in mouse models xenograft, syngeneic and PDX models (colon, gastric, renal and NETs). Developing of “tumor score” considering CXCR4 tumoral/TME signals. Evaluation of effector cell functions (Cell killing, migration or product-related toxicity cytokine release, primary immune cells using mass cytometry). • To develop GMP compliant procedures to manufacture clinical candidate tracer for imaging of CXCR4 positive tumors • “Proof of concept” Phase 1 Clinical Trial in solid cancer CXCR4 expressing. “Tumor score” CXCR4 tumoral/TME signals |
| Network | EuroNanoMed III |
| Call | Joint Transnational Call (2019) |
Project partner
| Number | Name | Role | Country |
|---|---|---|---|
| 1 | IRCCS - Istituto Nazionale tumori di Napoli Fondazione G. Pascale | Coordinator | Italy |
| 2 | cAix-Marseille University, French National Scientific Research Center (CNRS) | Partner | France |
| 3 | Vall d’Hebron University Hospital; Vall d'Hebron Institute of Research (VHIR) | Partner | Spain |
| 4 | Faculty of Medicine and Dentistry, Palacký University Olomouc | Partner | Czech Republic |
| 5 | Oslo University Hospital | Partner | Norway |