Tumor-specific concentration of effectors against cancer
It is possible to address multiple pathways of cancer with one poly functional molecule able to specifically reach and anchor on the tumour, recruit immune cells, reduce angiogenesis…This approach is at the core of the Nanomodule project, conducted by Affilogic and the Western Cancer Institute (Institut de Cancérologie de l’Ouest, Saint-Herblain, France).
In order to potentiate the anti-tumor response, the choice of Nanofitin modules to assemble focuses on those with activities involved in cancer synergistic signaling pathways. Their robustness limits the possibilities of their deactivation in the aggressive Tumor-Micro-Environment. The advantage of targeting such effectors towards tumor cells, over a cocktail approach, is a higher concentration of these effectors in the tumor-micro environment and limited side-effects due to fast systemic clearance of the Nanofitin-based biotherapy.
Different multispecific assemblies of Nanofitins are developed and tested, with for instance some data showing an increased cellular efficacy of anti-PDL1 Nanofitin® on EGFR+ tumor cells when fused to anti-EGFR Nanofitin®, or a positive impact of combining immune check-point inhibition (anti-PDL1 Nanofitin®) and expansion of anti-tumoral macrophages (anti-HSP110 Nanofitin®) to potentiate the anti-tumor response in vivo (Marcion et al., Nanofitins targeting HSP110: An innovative immunotherapeutic modality in cancer, International Journal of Cancer 2021). This work was performed in collaboration with INSERM (UMR1231), University of Bourgogne Franche-Comté, Anticancer Center Georges François Leclerc and the company Inovotion.
The NanoModule project was partially sponsored from January 2018 to December 2020 by a grant from the European Regional Development Fund (ERDF / FEDER) via the Region Pays de Loire (PL0015680).