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

2^2-INTRATARGET is a transnational European project with partners from Spain (coordinator), Italy, France and Norway. The consortium is composed of experts in antibody production, nanocarrier development, characterization of nanomedicines, immunology, pharmaceutics and cell biology. Research activities in the cancer field have resulted in development of new, highly potent cancer immunotherapies, based on antibodies and antibody fragments. These novel drugs are tailored to act inside cancer cells and inside immune cells. In spite of high research activity, these novel therapies have only limited use in the clinic, and they often give side effects and toxicity. One reason is that these drugs do not reach their intracellular targets. The main goal of 2^2-INTRATARGET is to develop multifunctional polymeric nanocarriers with the capacity to deliver antibody-based drugs to their target sites inside cancer or tumour associated immune cells. Novel antibodies towards selected targets located inside cancer or immune cells and involved in tumour growth and metastatic spread will be developed for interactions with oncoproteins leading to cancer cell death and for reprogramming immune cells from a tumour-promoting to a tumour-killing mode. In parallel, novel multifunctional nanocarriers suited for transport of these drugs into target cells will be developed. These nanocarriers will be designed to target two different tissue compartments, the primary tumour and its metastatic niche, e.g., in lymph nodes. All novel nanomedicines will be carefully characterized, and efficacy and toxicity tested in cell-based assays and in vivo in mouse models. Lung cancer with metastases, a highly aggressive cancer type with high mortality and low survival rates, will be used as test case for these novel nanomedicine products. Regulatory, ethical and market-related questions will be included in all steps of development. The consortium have had regular video meetings every third month, and a physical meeting was arranged at a consortium partner in Paris. In addition, there have been several meetings dedicated to discussions of results and progress, including the selection and effect of of antibodies to relevant targets located inside the cancer and immune cells. It has been challenging for the French partner to find and demonstrate effects of new antibodies with the expected effect on the target pathways in the cancer cells. The Spanish partner has developed a first generation of multifunctional polymeric nanocarriers, suited for encapsulation of antibody-based drugs and their targeted delivery inside cancer- and immune cells. SINTEF has worked on refining our methodology for characterization of uptake and effect in various cancer cells. SINTEF has received the first batches of nanocarriers from Spain and has evaluated the uptake and effect of these formulations in various selected cancer cell lines.

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2^2-INTRATARGET er et transnasjonalt Europeisk prosjekt med partnere fra Spania (koordinator), Italia, Frankrike og Norge. Konsortiet består av eksperter innen fremstilling av antistoff, nanobærerutvikling, karakterisering av nanomedisiner, immunologer, farmasøyter og cellebiologer. Forskning innen kreftbehandling har ført til utviklingen av nye potensielle kreftbehandlinger basert på antistoff og antistoff-fragmenter. Disse nye medikamentene er skreddersydd til å virke inne i kreftcellene og inne i immunceller. Til tross for høy forskningsaktivitet har slike behandlinger foreløpig kun begrenset anvendelse klinisk og de viser ofte et ugunstig effekt/toksisitetsforhold. En av årsakene er at disse medikamentene ikke når frem til det syke vevet og helt inn i målcellene. Hovedmålet med 2^2-INTRATARGET er å utvikle multifunskjonelle nanobærere som kan levere antistoff-baserte medikament inn i kreftceller og tumor-assosierte immunceller i to ulike typer sykdomsvev, primærtumoren og metastaser. Nye antistoff mot utvalgte mål i kreft- og immunceller sentral for tumorvekst og -spredning vil bli utviklet, samtidig som nye multifunksjonelle nanobærere, egnet til transport av slike medikament inn i målceller vil bli utviklet, både for interaksjoner med onkoproteiner som fører til kreftcelledød og for å reprogrammere immunceller fra å fremme tumorvekst til å hindre tumorvekst. Nanobærerne vil bli designet slik at de både når vev i primærtumor og metastaser i lymfeknutene. Alle nye nanomedisiner vil bli nøye karakterisert og effekt og toksisitet testet i celle-baserte analyser og in vivo i musestudier. Lungekreft med metastaser, en meget aggressiv krefttype med høy dødelighet og lave overlevelsesrater, blir brukt for å teste disse nye nanomedisinprodukter. Etter endt prosjekt håper man å ha utviklet 1-2 nye nanomedisinprodukter, klare for videreutvikling og kliniske studier. Regulatoriske, etiske og markedsmessige spørsmål blir inkludert på alle trinn av produktutviklingen.