Project: 2^2-INTRATARGET: Nanocarriers to deliver antibodies towards intracellular targets in cancer cells/TAMs at primary/metastatic sites

Acronym	INTRATARGET (Reference Number: EURONANOMED2020-145)
Duration	01/01/2021 - 01/01/2024
Project Topic	Antibody-based anticancer therapies, now regularly applied in the clinic, have represented a key breakthrough in oncology. Despite their recognized potential, marketed antibodies suffer of sub-optimal biodistribution at both tissue (primary tumor site and metastatic niches) and cellular level (cancer and immune cells). Importantly, a constrain of these antibodies is related to their inability to cross the cell membrane and reach intracellular oncoproteins. As a consequence, a significant number of intracellular drug targets remain still undruggable. Nanotechnology offers a great opportunity to make these targets druggable by facilitating the intracellular delivery of antibodies in the target tissues. The objective of this 2^2-INTRATARGET proposal is to address these challenges by engineering Multifunctional Polymeric Nanocarriers (MPNs) with the capacity to deliver antibody-based entities inside cancer cells or tumor associated macrophages (TAMs) in two different tissue compartments, the primary tumor and its metastatic niche (i.e. lymph nodes). The selected active candidates are full monoclonal antibodies (mAb), minibodies (miniAbs) and nanobody-fused-proteins (nAb-FP) against specific targets, KRAS, STAT3 and TGFb, which represent key pathways for tumor proliferation, metastatic spread and immune evasion. The combination of these potential nanomedicines is conceived as a multi-focal strategy that may represent the next milestone in the treatment of cancer. Our consortium is formed by 5 partners with complementary expertise in the fields of Nanomedicine, Antibodies and Cancer Immunotherapy. We have designed a working plan comprising: (i) development of antibody-based entities, mAb, miniAb and nAB-FP against selected targets; (ii) engineering and characterization of MPNs loaded with antibody-based entities; (iii) in vitro screening of MPNs using 2D and 3D models; (iv) in vivo antitumoral efficacy; (v) in vivo PK/BD studies and preliminary toxicology studies.
Network	EuroNanoMed III
Call	Joint Transnational Call (2020)

Project partner

Number	Name	Role	Country
1	Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Spain	Coordinator	Spain
2	Humanitas Clinical and Research Center (ICH), Italy	Partner	Italy
3	University of Navarra (UNAV), Spain	Partner	Spain
4	SINTEF Industry, Norway	Partner	Norway
5	HYBRIGENICS SERVICES	Partner	France