Verismo Therapeutics' Novel KIR-CAR Platform Shows Enhanced Safety and Efficacy in Solid Tumor Preclinical Studies
核心洞察
Verismo Therapeutics (搜索) presented preclinical data at SITC 2025 showing SynKIR™-110 (搜索) demonstrated reduced cell exhaustion and lower off-target toxicity compared to conventional CAR T therapies.
The novel KIR (搜索)-CAR platform achieved sustained tumor killing and deep regression in mesothelioma (搜索) mouse models while showing selective enrichment in tumors rather than normal tissues.
SynKIR™-110 (搜索) is currently in Phase 1 clinical trials for advanced ovarian cancer (搜索), cholangiocarcinoma (搜索), and mesothelioma (搜索), with FDA Orphan Drug and Fast Track designations for mesothelioma treatment.
Verismo Therapeutics (搜索) unveiled promising preclinical data for its lead CAR T therapy SynKIR™-110 (搜索) at the Society of Immunotherapy of Cancer (SITC) 2025 Annual Meeting, demonstrating superior safety and efficacy profiles compared to conventional CAR T approaches in solid tumor models. The oral presentation, selected as one of the top 150 abstracts from more than 1,300 submissions, highlighted the potential of the company's novel KIR (搜索)-CAR platform technology to address longstanding challenges in solid tumor treatment.
Enhanced Tumor-Specific Activity with Reduced Toxicity
The preclinical studies revealed that SynKIR™-110 (搜索), which targets mesothelin-expressing tumors, exhibited sustained killing of tumor cells while minimizing off-target activation and cytokine release in vitro. Unlike conventional 41BB-CD3ζ CAR T cells, SynKIR™-110 demonstrated reduced activation and exhaustion markers, suggesting decreased tonic signaling and functional exhaustion.
Dr. Nora Yucel, Principal Scientist at Verismo Therapeutics (搜索), presented the findings titled "A Novel NK-cell Based Split-Signaling Killer Immunoglobulin Receptor (KIR (搜索))-Based CAR T Targeting Mesothelin, SynKIR™-110 (搜索), Shows Increased Safety Profile and Increased Efficacy in vitro and in vivo."
Superior Performance in Preclinical Models
In NSG mouse models of mesothelioma (搜索), SynKIR™-110 (搜索) induced deep and prolonged regression of implanted tumors and metastatic spread. Notably, the therapy showed selective enrichment in tumors while being reduced in normal tissues, contrasting with the off-tumor accumulation in lung and normal tissues observed with conventional 41BB-CD3ζ CAR T designs.
"Conventional CAR T therapies have faced significant safety and efficacy challenges in treating solid tumors (搜索)," said Dr. Laura Johnson, CSO/COO of Verismo Therapeutics (搜索). "Our SynKIR™ platform presents a truly novel signaling platform approach designed to allow CAR T cells to rest and recover when not engaged with tumors, which in turn may reduce T cell exhaustion and improve safety and efficacy of tumor-specific killing."
Clinical Development and Regulatory Recognition
SynKIR™-110 (搜索) is currently being evaluated in a Phase 1 clinical trial (NCT05568680) in patients with advanced ovarian cancer (搜索), cholangiocarcinoma (搜索), and mesothelioma (搜索). The therapy has received both Orphan Drug and Fast Track Designations from the U.S. Food and Drug Administration (FDA) for the treatment of mesothelioma.
Novel KIR-CAR Platform Technology
The KIR (搜索)-CAR platform represents a multi-chain CAR T cell therapy that utilizes NK cell-derived KIR and DAP12 (搜索) split signaling to provide novel paired activation and co-stimulation separate from usual T cell stimulation pathways. This approach enables sustained chimeric receptor expression with improved long-term CAR T cell function and decreased T cell exhaustion, resulting in CAR T cell resistance to tumor immunosuppression and prolonged functional persistence.
Verismo Therapeutics (搜索), a subsidiary of HLB Innovation (搜索), is the only company developing the KIR (搜索)-CAR platform. The company has two assets in Phase 1 clinical trials: SynKIR™-110 (搜索) (NCT05568680) and SynKIR™-310 (NCT06544265), targeting areas of high unmet medical need including advanced solid tumors (搜索) and B cell associated disorders and malignancies.