Verifying a New Generation of Oncolytic Peptides as Cancer Immunotherapeutic Agents for Deep-Seated Tumors.

Leverkreft er en av de viktigste årsaken til kreftdødsfall over hele verden, hvor mer enn 600 000 pasienter dør årlig. Det er et stort behov for mer effektive behandlingsterapier, både med færre bivirkninger og lengre overlevelse. Dette prosjektet tar sikte på å verifisere en ny klasse onkolytiske peptider til bruk i lokal og / eller kombinasjonsimmunoterapi av primære og sekundære levermaligniteter, med vekt på hepatocellulært karcinom (HCC) og levermetastaser av kolorektal kreft (CRC). To nye peptider har blitt identifisert og in-vitro-studier har vist høye cytotoksiske aktiviteter mot et panel av forskjellige HCC- og CRC-cellelinjer. In vivo studier i ulike musemodeller har vist meget lovende resultater. Peptidene induserer tumorregresjon og en tumor-spesifikk immunrespons etter injeksjoner. Forhandlinger om kommersiell avtale pågår med industripartner angående videreføring av resultatene.

This project helped to increase the current understanding of various aspects of oncolytic peptide immunotherapy, e.g. peptide design, mode of actions, safety, etc. The project also contributed to the profile of Norwegian cancer research by strengthening networks with world leading institutions, e.g. the Gustave Roussy Institute, and by publishing research papers in high impact factor journals, e.g. Nature Cell Death and Disease. Using national popular science platforms, such as Forskning.no, awareness regarding liver cancer and current research was also increased. We currently negotiate with an industry partner regarding a commercial agreement. The industry partner will be responsible to bring the technology to market.

Liver cancer is the leading cause of cancer deaths worldwide, accounting for more than 600,000 deaths each year. There is a high unmet need for more effective therapies with fewer side effects and longer overall survival. This project aims to verify a new class of oncolytic peptides for use in local and/or combination immunotherapy of primary and secondary liver malignancies, with an emphasis on hepatocellular carcinoma (HCC) and liver metastases of colorectal cancer (CRC). Two new lead peptides have been identified. In vitro studies have been shown both peptides to have high cytotoxic activities against a panel of various HCC and CRC cell lines. Preliminary safety studies revealed that the peptides have low or no hypotensive effect. Mechanistic studies confirmed that both peptides induce immunogenic cell death, but they differ in mode of action. In vivo studies in different murine models have commenced and preliminary results are promising. Both peptides were shown to induce tumor regression and a tumor-specific immune response following intralesional injections. These studies will continue next year and their related work packages are scheduled to be completed by the end of 2018. Overall, the project is progressing in a satisfactory manner and important milestones have been reached. Subsequently the prognosis for 2018, the third and final year of the project, is promising.