METiS TechBio Advances mRNA Cancer Therapeutics with Dual Publications in Nature Communications and JITC
核心洞察
METiS TechBio (搜索) published breakthrough research on two mRNA-based cancer therapeutics, MTS-105 and MTS-107 (搜索), in Nature Communications and the Journal for ImmunoTherapy of Cancer respectively.
MTS-105, a first-in-class mRNA-encoded T cell engager for hepatocellular carcinoma (搜索), achieved 100% complete tumor clearance in mouse models at doses as low as 0.15 μg using liver-targeted delivery.
MTS-107 (搜索), an HPV16 (搜索)/18 therapeutic vaccine, demonstrated 100% complete response rates when combined with PD-1 (搜索) blockade in advanced tumor models.
METiS TechBio (搜索) announced the publication of two groundbreaking studies on its mRNA-based cancer therapeutics in leading peer-reviewed journals, marking significant advances in precision immunotherapy delivery. The research, published in Nature Communications and the Journal for ImmunoTherapy of Cancer (JITC), demonstrates the potential of the company's AI-powered NanoForge platform to overcome longstanding challenges in mRNA therapeutic delivery.
Revolutionary T Cell Engager Therapy for Liver Cancer
MTS-105 represents the world's first mRNA-encoded T cell engager (TCE) therapy for solid tumors, specifically targeting hepatocellular carcinoma (搜索) (HCC). Published in Nature Communications on December 15, the study titled "Organ-Specific Delivery of an mRNA-Encoded Bispecific T Cell Engager Targeting Glypican-3 (搜索) in Hepatocellular Carcinoma" reveals remarkable efficacy data.
The therapy employs a "Trojan Horse" strategy, delivering mRNA via liver-targeted lipid nanoparticles (LNPs) that translate in situ and secrete bispecific antibodies locally. In mouse models, MTS-105 achieved 100% complete tumor clearance at doses as low as 0.15 μg, dramatically outperforming protein-based TCE controls that achieved only approximately 50% tumor growth inhibition at 1 mg/kg (approximately 20 μg).
"MTS-105 is the first to show that an Fc-free bispecific T cell engager can activate T cells without driving exhaustion," said Dr. Wei XU, Chief Scientific Officer and corresponding author of both studies. The therapy demonstrated superior hepatic enrichment compared to antibody-based TCEs across multiple species, including mice, rats, and cynomolgus monkeys.
Safety profiles showed reduced systemic exposure and excellent tolerability in cynomolgus monkeys, with linear pharmacokinetics supporting potential weekly dosing. Cured mice remained tumor-free upon rechallenge, indicating durable T cell immune memory and prevention of recurrence. MTS-105 has now entered clinical development.
HPV Therapeutic Vaccine Shows Synergistic Potential
MTS-107 (搜索), an innovative mRNA therapeutic vaccine targeting HPV16 (搜索)/18-positive cervical and head and neck cancers, demonstrated equally impressive results in the JITC publication from September 17. The study, "mRNA-encoded mutant HPV16/18 vaccines promote specific T-cell responses and synergize with anti-PD-1 (搜索) checkpoint blockade in mediating therapeutic tumor regression in mice," showed 100% complete response rates when combined with PD-1 blockade in advanced HPV18 (搜索)⁺MC38 tumor models.
The vaccine utilizes spleen-targeted LNPs to deliver a construct combining dual E6 (搜索)/E7 (搜索) antigens with a novel immune-activating adjuvant. The design incorporates mutated HPV16 (搜索)/18 E6/E7 antigens with optimized mRNA sequences for improved translation and stability, while co-expressing GM-CSF to promote dendritic cell maturation and HPV-specific CD8⁺T cell activation.
Dr. XU noted the alignment with recent findings: "A recent Nature study reported that patients treated with PD-1 (搜索) inhibitors nearly doubled their three-year survival if they had also received an mRNA COVID-19 vaccine—a finding that strongly aligns with our observations for MTS-107 (搜索)."
AI-Powered Platform Technology
Both therapies leverage METiS's proprietary NanoForge platform, which introduces a precision-guided rocket-and-payload delivery system. The platform combines organ-targeted LNP delivery systems with programmable mRNA engineering to activate antitumor immunity in specific organs.
"Our NanoForge engine significantly accelerates LNP and mRNA design cycles, boosting delivery efficiency and safety for liver- and spleen-targeted therapeutics," stated Dr. Andong LIU, Vice President and Head of Platform Technologies, and co-corresponding author of the Nature Communications study.
Chris LAI, Co-founder and CEO, emphasized the clinical significance: "In conventional cancer therapy, most 'soldiers' remain outside the tumor, unable to infiltrate solid tumors for precise, effective killing. Our 'rocket-and-satellite' precision delivery paradigm has been strongly validated in these studies."
Clinical Development Pathway
MTS-105 has entered clinical development as a first-in-class therapy, while MTS-107 (搜索) will continue into clinical exploration. The organ-specific delivery approach addresses fundamental challenges in mRNA therapeutics, particularly the delivery limitations that have constrained the field's potential.
The research establishes METiS's position at the intersection of AI-driven nanodelivery and tumor immunotherapy, with both programs representing potential breakthrough treatments for their respective cancer indications. The company plans to advance global clinical development with partners, aiming to bring these targeted therapies to patients.