IMoST - Pre-targeted radioimmunotherapy

Published on June 8, 2021 – Updated on July 20, 2021

The project consists in developing radiolabelled/fluorescent probes and studying their recognition against a functionalized monoclonal antibody in an immunotargeting context. The multimodality aspect of this imaging/therapeutic approach and the different antibodies used make it a potentially universal strategy.

Bioluminescence imaging in an orthotopic peritoneal model (A431-CEA-Luc) after injection of NaCl, [177Lu]Lu-Tz-2 (40 MBq) or PRIT (50 µg of anti-CEA-TCO followed by 40 MBq of [177Lu]Lu-Tz-2 at 24h).

Bioluminescence imaging in an orthotopic peritoneal model (A431-CEA-Luc) after injection of NaCl, [177Lu]Lu-Tz-2 (40 MBq) or PRIT (50 µg of anti-CEA-TCO followed by 40 MBq of [177Lu]Lu-Tz-2 at 24h).

Monoclonal antibodies (mAbs) are highly selective and effective drugs for improved patient care, particularly in oncology. In combination with a toxin, enzyme or active substance, they are also capable of contributing to the selective destruction of tumour cells. Given their tumour specificity, their association with a radionuclide may therefore constitute a very promising theranostic approach. However, their high molecular weight slows their blood clearance, which may induce haematological and bone marrow radiotoxicity. The immune-pretargeting approach consisting in dissociating the probe from the mAb, while allowing its ligation at the tumour level, is a promising approach for a theranostic application in a nuclear medicine (PMID: 31588245).


This project is therefore based on several objectives:

  • To amplify the molecular signal by developing dendronised probes (project supported by CAP20-25 for 2019-2020)
  • To address gold/silica hybrid radiosensitizing nanoparticles in a specific way (supported by CLARA 2019-2020)
  • To develop a universal kit for the functionalization of mAbs with bioorthogonal entities for application in a hospital (supported by the Ligue Régionale Contre le Cancer 2021-2022)
  • To develop a theranostic stratification tool for patients eligible for targeted therapy

We are working with mAbs targeting EGFR, HER2 and CD20.

These different approaches are developed in collaboration with academic and socio-economic partners in the AURA region, and in the Bourgogne region.
 

Other GCCA Partners

  • Jean PERRIN Comprehensive Cancer Center - Nuclear Medicine Department