NEXTGENESIS (therapy)

NEXTGENESIS (therapy)

The NEXTGENESIS project aims to revolutionize intraoperative cancer diagnostics and therapy using the SpiderMass technology. It builds upon previous developments to:

  1. Conduct the first-in-human clinical trial using SpiderMass.
  2. Extend SpiderMass capabilities into photodynamic therapy (IROSMASS) and minimally invasive surgery (MAESTRO).

NEXTGENESIS extends SpiderMass technology beyond diagnostics into therapeutic and surgical applications.
IROSMASS pioneers a novel, photosensitizer-free ROS-based cancer treatment.
MAESTRO introduces a soft robotic system with AI-driven real-time molecular imaging, enabling minimally invasive, autonomous cancer surgery.
By integrating real-time molecular imaging, robotics, and AI, NEXTGENESIS represents a paradigm shift in surgical oncology, paving the way for more precise, efficient, and safer cancer treatments.

Key Research Axes

Clinical Trials with SpiderMass (MESSIDORE & RHU SpiderMass)

Surgical oncology relies on precise tumor margin identification to ensure complete cancer removal while preserving healthy tissue. Current intraoperative techniques, such as frozen section analysis, are time-consuming and may lack real-time precision. SpiderMass, a novel real-time mass spectrometry-based technology, offers a non-destructive approach to intraoperative molecular tissue analysis. The NEXTGENESIS project aims to validate SpiderMass in a clinical setting, particularly for sarcoma and ovarian cancer surgeries.

Key Objectives

  • Validate SpiderMass technology in a clinical setting for cancer surgery.
  • Conduct a first-in-human trial to assess real-time intraoperative tumor margin delineation.
  • Compare SpiderMass results to the gold standard (extemporaneous examination).
  • Demonstrate the feasibility of integrating SpiderMass into the operating room.

Innovations and Progress

  • Prototype Installation: A SpiderMass prototype will be installed at CLCC COL to perform ex vivo intraoperative tissue assessment.
  • Clinical Validation in Sarcoma Surgery: The MESSIDORE project will compare SpiderMass vs. standard pathology to ensure equal or superior accuracy.
  • Integration into Surgery: After ex vivo validation, the SpiderMass prototype will be moved into the operating room for a first-in-human trial.
  • Expansion to Ovarian Cancer: As part of the RHU SpiderMass project, the technology will also be evaluated for ovarian cancer surgery.

IROSMASS – Direct PhotoActivation (DPA) for Cancer Therapy

Conventional cancer therapies often suffer from off-target toxicity and resistance mechanisms. Photodynamic Therapy (PDT) has shown promise but requires photosensitizers that limit its applicability. The IROSMASS project proposes an innovative Direct PhotoActivation (DPA) therapy, where a 765 nm laser generates Reactive Oxygen Species (ROS) directly within tumor cells, inducing targeted cell death. This novel approach aims to offer a safer and more effective cancer treatment, particularly in combination with immune-based therapies like CAR-MAC therapy.

Key Objectives

  • Develop a Direct PhotoActivation (DPA) therapy using 765 nm light to generate Reactive Oxygen Species (ROS) and induce cancer cell death.
  • Validate the safety and effectiveness of this approach in tumor cells vs. healthy tissues.
  • Integrate IROSMASS with SpiderMass technology for real-time assessment of cancer therapy effectiveness.
  • Combine IROSMASS with CAR-MAC therapy for a dual therapeutic approach.

Innovations and Progress

  • Development of 765 nm DPA Therapy: Unlike traditional Photodynamic Therapy (PDT), IROSMASS will use direct laser activation without a photosensitizer.Preclinical Validation Pipeline:
  • Cellular models: Breast cancer cell lines and primary macrophages.
  • Spheroid and organoid models: Tumor-macrophage co-cultures to test selective cytotoxicity.
  • Mouse models: Triple-negative breast cancer models to validate in vivo effectiveness.
  • AI-based Molecular Profiling: Machine learning models will classify molecular changes before and after 765 nm irradiation to assess therapy effectiveness.
    Integration with CAR-MAC Therapy: Combining IROSMASS with engineered macrophage-based therapy to enhance tumor killing while preserving immune cells.

    MAESTRO – Soft Robotics for Minimally Invasive Surgery

    Minimally invasive surgery (MIS) has revolutionized surgical procedures by reducing trauma, recovery time, and post-operative complications. However, current robotic systems lack the flexibility and real-time molecular imaging capabilities needed for precise tumor resection. The MAESTRO project aims to develop an innovative soft robotic system (SR) designed for endoscopic and laparoscopic procedures, integrating real-time molecular imaging (SpiderMass MSI), AI-driven guidance, and augmented reality (AR) for enhanced surgical decision-making. By combining soft robotics with molecular imaging, MAESTRO will significantly improve the accuracy and safety of tumor resection.

    Key Objectives

    • Develop a soft robotic system (SR) optimized for endoscopic and laparoscopic procedures.
    • Integrate real-time molecular imaging (SpiderMass MSI) into the soft robot for intraoperative cancer diagnostics.
    • Implement AI-driven guidance for precise tumor detection and resection.
    • Enhance surgical decision-making with Augmented Reality (AR) navigation and digital twins.

    Innovations and Progress

    • Soft Robotic System Development:
      • Collaboration with Inria-DEFROST to develop a silicone-based flexible robotic system.
      • Compatibility with laparoscopy, endoscopy, and colonoscopy for minimally invasive procedures.
    • AI-Guided Molecular Imaging:
      • SpiderMass MSI will provide real-time molecular analysis of tissues during surgery.
      • AI models (ANR DEADPOOL project) will classify tumor margins for improved surgical precision.
    • Augmented Reality Integration:
      • Digital twin technology will create a 3D map of tumor margins using SpiderMass data.
      • Instant feedback will guide surgeons in real-time tumor removal.
    • Autonomous Navigation and Decision Support:
      • The robotic system will allow for precise, non-contact molecular imaging.
      • AI-driven electromagnetic navigation will help the system identify suspect regions for further analysis.