19457
Overview
Many solid tumors evade immune attack through tumor-associated macrophages (TAMs) that suppress T-cell activity. We designed a TREM2-IL2 immunocytokine with robust anti-tumor activity achieved by inhibition of tumor-associated macrophages, boosted by local activation of T and NK cells through IL-2. Drug safety is ensured by local IL-2 activation only in the tumor microenvironment. TREM2-IL2 is designed to overcome key resistance mechanisms and show efficacy in refractory tumors.
Applications
- Immunotherapy for solid tumors, including immune-checkpoint-inhibitor (ICI)-resistant cancers
- Combination therapy with anti-PD-1/PD-L1 or other immune modulators
Differentiation
- Dual mechanism: combines TREM2 blockade with localized cytokine activation
- Tumor-restricted activity: activated only by a TAM protease (MMP14)
- Superior efficacy: outperforms PD-1 or TREM2 monotherapies or combination therapy
- Safe and potent: strong anti-tumor effects without cytokine-induced toxicity
Development Stage
- Demonstrated potent monotherapy anti-tumor efficacy in MC38 colorectal cancer and MCA205 fibrosarcoma mouse models with no toxicities or off-target immune activation
- Validated by scRNA-seq and various functional assays demonstrating potent myeloid, T and NK cell activation in patient-derived tumor fragments from renal cell carcinoma (RCC) patients
References
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