Project: Targeting breast tumors with anti-Netrin-1 nanocarriers as a promoter of immunity ?

Acronym	NanoNET (Reference Number: EURONANOMED2019-135)
Duration	01/01/2020 - 31/12/2022
Project Topic	Immunotherapy with checkpoint inhibitors is currently revolutionizing cancer treatment in clinic, but only a fraction of patients shows response. Triple negative breast cancer is a subtype extremely aggressive and in most of the case it is not responsive to immunotherapy. An urgent need of new treatments is thus essential to cure this disease. To escape cell death, cancer cells secrete survival factors like Netrin-1. We took advantage of an anti-Netrin-1 antibody (NP137), now tested in a phase I clinical trial (first-in-man-first-in-class ; NP137, clinicaltrial.gov: NCT02977195) to imagine a co-therapy who will combine a new nano-approach with the futures standard of care used in clinic. In our NanoNET project, NP137 antibody will be linked through specific engangers to chemotherapy-loaded polyethylene glycol(PEG)ylated nanocarriers to specifically target the tumor microenvironment. The drug released will induce apoptosis in tumor cells and potentially in immunosuppressive cells, inducing immune reactivity so improving the effects of checkpoint inhibitors. The objectives of the project are (1) Design and produce bispecific PEG-engagers who will be generated by genetically fusing the NP137 antibody against Netrin-1 to anti-PEG antibodies. The NP137-engagers created will bind nanocarriers containing PEG to selectively target them (2) to validate these molecule for specificity and bio-distribution, (3) to study combinations of NP137-NanoNets/ Immunotherapy in vivo to analyse the effect on cancer growth on mice syngeneic models, and (4) to investigate the underlying mechanisms on the immune system and determine the immune population implicated in the anticancer response.
Network	EuroNanoMed III
Call	Joint Transnational Call (2019)

Project partner

Number	Name	Role	Country
1	Claude Bernard Lyon 1 University	Coordinator	France
2	Academia Sinica	Partner	Taiwan
3	Istituto Oncologico Veneto IOV-IRCCS	Partner	Italy
4	Netris Pharma	Partner	France