Is tetraspanin 8 a target for radioimmunotherapy in syngeneic APC/min colorectal cancer model ?

International audienc

Conception et validation préclinique de nanobodies radiomarqués dirigés contre HER3 dans le cancer du sein triple négatif

International audienc

Proteoglycans as Target for an Innovative Therapeutic Approach in Chondrosarcoma: Preclinical Proof of Concept

International audienceTo date, surgery remains the only option for the treatment of chondrosarcoma, which is radio-and chemoresistant due in part to its large extracellular matrix (ECM) and poor vascularity. In case of unresectable locally advanced or metastatic diseases with a poor prognosis, improving the management of chon-drosarcoma still remains a challenge. Our team developed an attractive approach of improvement of the therapeutic index of chemotherapy by targeting proteoglycan (PG)-rich tissues using a quaternary ammonium (QA) function conjugated to mel-phalan (Mel). First of all, we demonstrated the crucial role of the QA carrier for binding to aggrecan by surface plasmon resonance. In the orthotopic model of Swarm rat chondrosar-coma, an in vivo biodistribution study of Mel and its QA derivative (Mel-QA), radiolabeled with tritium, showed rapid radioactivity accumulation in healthy cartilaginous tissues and tumor after [ 3 H]-Mel-QA injection. The higher T/M ratio of the QA derivative suggests some advantage of QA-active targeting of chondrosarcoma. The antitumoral effects were characterized by tumor volume assessment, in vivo 99m Tc-NTP 15-5 scinti-graphic imaging of PGs, 1 H-HRMAS NMR spectroscopy, and histology. The conjugation of a QA function to Mel did not hamper its in vivo efficiency and strongly improved the toler-ability of Mel leading to a significant decrease of side effects (hematologic analyses and body weight monitoring). Thus, QA conjugation leads to a significant improvement of the therapeutic index, which is essential in oncology and enable repeated cycles of chemotherapy in patients with chondrosarcoma

Triazoles from N-alkynylheterocycles and their coordination to iridium

N-alkynylheterocycles (benzimidazole and indazole) are converted to triazoles by click chemistry, and the resulting triazoles react with [IrCl2Cp*]2. The benzimidazole-triazole coordinates in a monodentate fashion through the benzimidazole, whereas the indazole-triazole is bidentate through coordination of both heterocycles. Reaction of the benzimidazole-triazole with methyliodide gives a benzimidazolium salt that deprotonates on coordination to afford a rare example of a bidentate NHC–triazole