monalizumab

Overview

Monalizumab is a humanized anti-NKG2A (KLRC1) monoclonal antibody that blocks the inhibitory NKG2A/HLA-E axis, restoring NK cell and CD8+ T cell cytotoxic activity against HLA-E-expressing tumor cells. It is being investigated as an early cancer interception strategy.

Evidence in the corpus

• HLA-E upregulation was identified in fallopian tube p53-signature and STIC (serous tubal intraepithelial carcinoma) precursor lesions to high-grade serous ovarian carcinoma (HGSOC), suggesting that anti-NKG2A antibodies such as monalizumab could be a promising strategy for early interception in high-risk patients with incidental STICs PMID:39386723.
• Multimodal spatial profiling showed NK cells become nearly undetectable in later stages (STIC and cancer), while HLA-E is upregulated progressively; this immune evasion axis represents the mechanistic rationale for NKG2A blockade PMID:39386723.

Resistance mechanisms

• NK cell depletion in advanced STIC/HGSOC lesions may limit the efficacy of NKG2A-targeted therapy at late disease stages; early intervention is the proposed therapeutic window PMID:39386723.

Cancer types (linked)

• HGSOC

Sources

• PMID:39386723

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