RESYNC · Functional chemical reprogramming of cancer cells to induce antitumor immunity

THE CHALLENGE: Immunotherapy has revolutionized cancer treatment but most patients do not respond due to immune evasion mechanisms, including heterogeneity and lack of tumor antigen presentation. Moreover, these therapies have met limited success in the treatment of solid tumors and are frequently associated with severe adverse effects.RADICAL VISION: The radical vision of the RESYNC consortium is to revolutionize cancer immunotherapy through small-molecule (SM)-based reprogramming of cancer cells into immunogenic (neo)antigen-presenting dendritic cells type 1 (cDC1) to elicit a personalized anti-tumor immunity. Cell reprogramming will be coupled with nanoparticle formulations enabling safe, low cost and efficient systemic targeting of disseminated tumors. The proposed platform will enable breakthrough innovations in the cellular reprogramming-based therapeutics space and have a broad and disruptive effect on the immune-oncology therapeutics scientific field and market. With a complementary consortium, we expect to achieve proof-of-concept for chemical cDC1 reprogramming by the end of the project (2026).IMPACT: This approach will for the first time harness the full potential of cellular reprogramming to induce immunity against tumour antigens with the tractability of systemic delivery of cDC1-inducing SMs. This project will result in next generation platforms for in vivo reprogramming and cell-targeted delivery of SMs with high cell specificity, low price and improved safety. SM-mediated antigen presentation will be combined with immune checkpoint blockade enabling immunotherapy in all patients. Ultimately, this project will set the stage for a new era of personalized, off-the-shelf cancer immunotherapies.