Colorectal cancer (CRC) is the 2nd leading cause of cancer death, claiming the lives of about 250.000 Europeans annually. CRC patients could greatly benefit from cell-based immunotherapy: dendritic cells (DC) or cytolytic cells. Herein, immune cells are endowed with therapeutic response programs to treat the disease. Still, issues related to the vector, delivery platform and cost loom large.

 In CHIMERNA, a European collaborative transdisciplinary consortium of academic and clinical partners, located in Belgium, France and Spain, aims to advance in situ immune cell engineering by generating knowledge and an affordable modular platform based on key enabling technologies (KET) of each academic partner: mRNA engineering (VUB), mRNA nanoformulation (IQS), and controlled release hydrogels (UA). Value beyond the sum of the individual KET will be created by means of smart design of the project and end product: a Hydrogel Immunomodulatory Therapy (HIT).

HIT consists of an injectable lipid-based hydrogel that contains chemokines to attract the desired immune cells and targeted stealth polymeric mRNA-loaded nanoparticles to transfect these cells with optimized mRNA coding therapeutic response programs, hence HIT acts as a hub for in situ immune cell engineering. In 7 work packages, CHIMERNA will deliver a proof-of-concept (PoC) on the joint approach, focusing on DC engineering for therapeutic neoantigen vaccination in CRC. Building on the partners’ strengths and advances in next-generation sequencing, CHIMERNA includes genomic profiling-based precision medicine, designing and evaluating the most appropriate vaccine for individual cancer patients in a phase I clinical trial (IDIBAPS). By the end of the project, we expect to have a PoC for potent DC vaccination in CRC, while the modularity of the approach can be used to attract and reprogram any immune cell or treat diseases beyond cancer (e.g., autoimmunity, infectious diseases), thereby creating a large impact on health.