Pre-clinical evaluation of novel product candidates as targeted cancer therapeutics. Specificity, bio-distribution and therapeutic efficacy

The aim of the studies performed in this Ph.D. project has been to develop and test Oncoinvent's novel product candidates for cancer therapy. The main technological platform for this development is to use radionuclides to irradiate cancer cells so that they either die or cease to divide. Radionuclides can be combined with a carrier compound whose task is to maintain the radioactivity and transport it to the area of the body where the cancer grows. In this project, both antibodies and microparticles have been studied as carriers of radionuclides with the purpose of determining a good combination of these, both in relation to their properties and the disease situation in patients. The results of these pre-clinical studies have been the selection of the product candidate Radspherin® which is specifically designed for treatment of metastatic cancer in body cavities. Radspherin® is a microparticle loaded with a radionuclide emitting alpha-radiation. The alpha-radiation has very high energy and a range in tissue of only 50-100 micrometers. Thus, only cells that are in the immediate vicinity of the microparticles are irradiated while at the same time deeply penetrating radiation which can damage healthy organs and tissues are avoided. During the project period, experiments have been performed showing that Radspherin® reduces tumor growth and increases the survival of mice with cancer in the peritoneal cavity. No side effects have been observed in mice, indicating that the treatment is safe and well tolerated. The studies in this project have been part of the basis for the growth and development Oncoinvent has had, and the company is now in the process of entering Radspherin® into the first part of clinical trials. The project was carried out in collaboration with the University of Oslo and Oslo University Hospital.

Virkninger: -Kompetansehevning hos kandidat, internt i firma, hos samarbeidspartnere, og internasjonalt i forhold til nye produkter og ny kunnskap for alfa-emitterende kreftbehandling -Kompetansehevning hos næringslivspartnere og investorer rundt utvikling av radiofarmasøytiske produkter Effekter: -Virkningene over vil også være langsiktige mht kompetansen oppnådd i forskningsfeltet og i næringslivet -Potensielle helsefremmende effekter hos kreftpasienter under kliniske studier og ved en markedslansering -Næringslivsutvikling innenfor terapeutisk bruk av alfa-emitterende radioisotoper

The Ph.D. project will be a part of pre-clinical evaluation and documentation of the therapeutic compounds of Oncoinvent AS (OI-candidates). Oncoinvent AS is a R&D intensive company that develops novel product candidates for targeted cancer therapy. The main technical platform for the drug development is the use of targeting device, such as monoclonal antibodies in combination with effector functions such as immune effector recruiting protein sequences and radionuclides. The company intends to develop n ovel candidates (OI-candidates) for both targeted immunotherapy and radio-immunotherapy. The Ph.D. Project will include studies of tumor cell specificity and of cytotoxic potential of OI- candidates in vitro. The Project will also include studies in mic e to evaluate in vivo specificity, bio-distribution, therapeutic efficacy and safety. The main product candidates in development are the antibodies OI-1 and OI-3. These antibodies selectively target a broad range of human cancers including osteosarcoma , melanoma, sub-types of breast cancers, pancreatic carcinoma and prostate cancer. The OI-variants ability to recruit immune effector cells, as well as their potency as carriers for radionuclide payloads aiming for potent and selective targeted cell kill will be assed. Murine xenograft models have been established with relevant human tumor cell lines at the Institute of Cancer Research, Department of Tumor Biology