Carisma Therapeutics Highlights Engineered Macrophage Success In Liver Fibrosis Treatment At AASLD 2024

Carisma Therapeutics Inc., a clinical-stage biopharmaceutical leader in immunotherapy innovation, unveiled encouraging preclinical findings on its engineered macrophages for liver fibrosis at the 2024 American Association for the Study of Liver Diseases (AASLD) The Liver Meeting®. These results highlight the potential of Carisma’s macrophage-based approach to address liver fibrosis across various models, offering an off-the-shelf treatment possibility for patients battling fibrotic liver conditions, including advanced metabolic dysfunction-associated steatohepatitis (MASH).

Liver fibrosis, a hallmark of advanced liver diseases such as MASH, acute liver injury, and primary biliary cholangitis, arises from chronic inflammation, impaired efferocytosis (the clearance of dead hepatocytes by macrophages), and excessive collagen buildup driven by hepatic stellate cell activation. Despite its prevalence, treatment options for advanced liver disease remain scarce, making Carisma’s engineered macrophages a promising step toward addressing these unmet medical needs.

Michael Klichinsky, PharmD, PhD, Co-founder and Chief Scientific Officer of Carisma, said in a statement, "We are pleased to present compelling preclinical data supporting the therapeutic potential of our engineered macrophages to address a critical unmet need in liver fibrosis, which is found in advanced stages of MASH. These data underscore the efficacy of our engineered macrophages as a differentiated, off-the-shelf approach for treating advanced liver fibrosis. Based on these promising findings, we are committed to advancing our liver fibrosis program.”

New preclinical data reveal that macrophages can be genetically programmed to target critical pathways driving liver disease. By incorporating factors such as TIM4 (to restore efferocytosis), relaxin (to suppress hepatic stellate cell activation), and IL10 (to mitigate inflammation), these engineered macrophages demonstrate significant therapeutic potential. 

In the choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) model of MASH—a highly translational framework—a single dose of macrophages expressing TIM4, either alone or combined with relaxin, markedly reduced liver fibrosis and stellate cell activation. Furthermore, the engineered macrophages exhibited superior efficacy compared to non-engineered counterparts and were well-tolerated across all tested models.