New preclinical data from Verismo Therapeutics’ lead clinical pipeline, SynKIR™-110, targeting mesothelin in solid tumors, were presented at the Society of Immunotherapy of Cancer (SITC) 2025 Annual Meeting, held November 5 – 9 in the Gaylord National Resort and Convention Center, National Harbor, Maryland.
Mesothelin (MSLN) is an attractive target for CAR T cell therapy in solid tumors, as it is overexpressed in tumors compared with normal tissues.
The oral presentation, selected as one of the top 150 abstracts out of more than 1,300 submissions, showcased the latest preclinical data demonstrating SynKIR™-110’s improved safety profile and enhanced anti-tumor activity compared to conventional CAR T therapies.[1]
A Novel NK-cell Based Split-Signaling Killer Immunoglobulin Receptor (KIR)-Based CAR T Targeting Mesothelin, SynKIR™-110 Shows Promissing Results.
Highly effective
The KIR-CAR platform is a multi-chain CAR T cell therapy that has shown highly effective, prolonged solid tumor treatment in otherwise CAR-resistant preclinical animal models with challenging tumor microenvironments.
Using NK cell-derived KIR and DAP12 split signaling provides a novel paired activation and co-stimulation separate from the usual T cell stimulation pathways.
KIR-CAR enables sustained chimeric receptor expression with improved long-term CAR T cell function and decreased T cell exhaustion.
This results in CAR T cell resistance to tumor immunosuppression, prolonged functional persistence, and improved tumor elimination. Together, this platform offers the potential to enhance CAR T treatment in both solid and hematologic tumors.
Key Findings
The study results demonstrated:
- Enhanced Tumor-Specific Serial Killing: In vitro, SynKIR™-110 showed sustained killing of MSLN-expressing tumor cells while minimizing off-target activation and cytokine release.
- Reduced Exhaustion and Improved Functional Persistence: Unlike conventional 41BB-CD3ζ CAR T cells, SynKIR™-110 exhibited reduced activation and exhaustion markers in vitro, suggesting less tonic signaling and functional exhaustion.
- Improved Anti-Tumor Activity: In NSG mouse models of mesothelioma, SynKIR™-110 induced deep, prolonged tumor regression and prevented metastatic spread.
- Less Off-tumor Activity: SynKIR™-110 cells were selectively enriched in tumors and 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,” noted Laura Johnson, M.Sc., Ph.D., Chief Scientific Officer of Verismo Therapeutics.
“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,” Johnson concluded.
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Clinical trials
SynKIR-110 for Mesothelin-Expressing Ovarian Cancer, Cholangiocarcinoma or Mesothelioma
ClinicalTrials.gov ID NCT05568680
SynKIR-310 for Relapsed/Refractory B-NHL – ClinicalTrials.gov ID NCT06544265
Reference
[1] Yucel N, Nunez-Cruz S, Leferovich J, Truong T, Blair M, Xu J, et al. 298 A novel NK-cell based split-signaling killer immunoglobulin receptor (KIR)-based CAR T targeting mesothelin, SynKIR-110, shows increased safety profile and increased efficacy in vitro and in vivo. Journal for ImmunoTherapy of Cancer. 2025;13:. https://doi.org/10.1136/jitc-2025-SITC2025.0298 [Article]
Featured image:Licensed under the Unsplash+ License.
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