Myeloid Therapeutics announced groundbreaking first-in-human clinical data for its in vivo mRNA CAR therapies at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, representing a significant milestone in RNA-based immuno-oncology. The company presented data on MT-302 and MT-303, which embody the first clinical applications of systemically administered in vivo mRNA CAR therapies.
Revolutionary Approach to CAR Therapy
"Our presentations at ASCO demonstrate the clinical translation of our proprietary mRNA-LNP platform for in vivo immune cell engineering," said Daniel Getts, PhD, CEO and Co-founder of Myeloid Therapeutics. "With MT-302 and MT-303, we are pushing beyond the limits of traditional CAR therapies—removing the need for often complicated ex vivo manipulation while delivering potent, tumor-specific immune activation in patients with advanced solid tumors."
The initial translational results support proof-of-mechanism with immune reprogramming resulting in tumor penetration and pro-inflammatory alteration in the tumor microenvironment (TME). This approach represents a fundamental shift from traditional CAR-T therapies that require complex ex vivo cell manipulation.
MT-302: TROP2-Targeted Therapy Shows Promise
MT-302 is the first intravenously delivered mRNA-based CAR therapy to enter clinical trials. The therapy uses synthetic mRNA encapsulated in lipid nanoparticles (LNPs) to reprogram circulating immune cells in vivo to express a TROP2-targeted CAR.
Key findings from the MT-302 Phase 1 study include immune activation demonstrated through single-cell RNA sequencing, which showed selective CAR expression in myeloid cells and increased pro-inflammatory gene signatures across tumor types. Pharmacodynamic markers confirmed successful delivery and CAR expression following systemic administration, while dose escalation continues with an optimized linear mRNA based on preclinical demonstration of expression beyond 12 days.
MT-302 is a first-in-class, TROP2-FcA-LNP targeting TROP2, which is overexpressed in many epithelial tumors and corresponds with low expression in healthy tissues. The therapy has demonstrated promising preclinical results including robust expression in myeloid cells and a favorable safety profile in rodents and non-human primates.
MT-303: Targeting Hepatocellular Carcinoma
MT-303 represents an innovative in vivo CAR therapy specifically designed to reprogram Fc receptor gamma chain-expressing myeloid cells to recognize and destroy GPC3+ tumor cells following intravenous mRNA-LNP administration. The ongoing multicenter, open-label Phase 1 trial in advanced solid tumors expressing GPC3, including hepatocellular carcinoma, employs a Bayesian Optimal Interval (BOIN) dose escalation design.
The mRNA encodes a GPC3-targeted CAR construct driven by CD89, restricting expression to myeloid cells. MT-303 is a first-in-class, GPC3-FcA-LNP targeting glypican-3 (GPC3), which is overexpressed in most human hepatocellular carcinomas and exhibits limited expression in healthy tissues.
Clinical Validation and Future Implications
"These data show that we can deliver repeated doses of LNP-mRNA in patients demonstrating that CAR-programmed myeloid cells can penetrate solid tumors and alter the tumor microenvironment (TME), which opens up multiple avenues for potential clinical benefit moving forward," said Matt Maurer, MD, Chief Medical Officer of Myeloid Therapeutics.
The results offer early validation of Myeloid's platform technologies and could ultimately change how solid tumors are treated, offering patients a more accessible, potentially more tolerable, and highly targeted therapy option without the burdens associated with traditional cell therapies.
Unlike other therapies, both MT-302 and MT-303 bring the potential advantages of eliciting a full immune response by also presenting tumor neoantigen to stimulate T cells. Myeloid expects to share additional clinical translational data at an upcoming medical meeting upon completion of the Phase 1 studies of MT-302 and MT-303.
