Cellular reprogramming emerged as a promising gene therapy approach for several diseases, in particular regenerative medicine and cancer. To date, cellular reprogramming is commonly achieved using transcription factors delivered by viral vectors, including lentivirus and adenovirus, which allow repeated administration but pose the risk of integrative oncogenesis. Additionally, viral vectors have complex and costly manufacturing processes, limiting their wide applicability.
Small molecules (SM) emerge as promising new candidates to induce cell conversion as they circumvent the safety concerns associated with viral vectors and the limitations of other approaches (e.g.: RNA-based approaches). The radical vision of the RESYNC consortium is to revolutionize cancer immunotherapy through SM-based reprogramming of cancer cells into immunogenic cancer antigen-presenting type 1 conventional dendritic cells (cDC1) to elicit personalized anti-tumor immunity. It envisions to overcome the barriers of current immunotherapies (e.g. lack of clinical response in most patients, safety, high costs and complex manufacturing), through a safe and cost-efficient platform for systemic cancer cell functional reprogramming leveraging SM mimicking transcription factors for reprogramming. By counteracting immune evasion mechanisms, our proposed breakthrough can result in novel therapeutic strategies based on the systemic administration of cancer-targeted SM cocktails to 1) induce personalized anti-tumor immunity as standalone treatment, and 2) synergize with existing immunotherapies to increase their effectiveness. By avoiding the caveats of current ex vivo and viral vector-based reprogramming strategies, our technology has the potential to be quickly adopted and widely applicable in the clinic.
