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Human Monoclonal Antibody against hIL18 Receptor Accessory Protein Chain Promotes Anti-Tumor Activity in

Fang Hu¹, Yonggang Wang¹, Guowei Qian¹

¹Department of Oncology, Affiliated Sixth People's Hospital, Shanghai Jiaotong University, Shanghai, China.

Annals of Clinical and Laboratory Science

|February 3, 2026

Abstract

Objective:

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that lacks effective targeted therapies. The interleukin-18 (IL-18) signaling pathway contributes to cancer progression and poor survival outcomes in several tumor types, including TNBC. IL-18 receptor accessory protein chain (IL-18RAcP), binding to the IL18/IL18Rα complex, plays a critical role in initiating and transducing IL-18 signaling. Targeting IL-18RAcP with human antibodies may offer a promising therapeutic strategy for TNBC.

Methods:

Human single-chain variable fragment (scFv) antibodies targeting IL-18RAcP were screened via phage display and characterized using ELISA, SPR, and crystallography. The functional assays that were used included qRT-PCR, MTT, Western blotting, flow cytometry, and xenograft models. Binding interactions were further validated through yeast two-hybrid assays and structural analysis.

Results:

We found that elevated IL-18RAcP expression in TNBC is associated with poor recurrence-free survival (RFS), suggesting its potential as both a clinical marker and a therapeutic target. Using combinatorial scFv antibody phage display libraries, we identified a human monoclonal antibody, scFvAPC10, which binds IL-18RAcP with high affinity. scFvAPC10 significantly inhibits TNBC cell proliferation in vitro and reduces tumor growth in vivo by inducing apoptosis. Mechanistic studies reveal that scFvAPC10 impairs both NF-κB and MAPK signaling pathways. Structural analysis shows that scFvAPC10 interacts with the D1-D2 domains of IL-18RAcP through three hydrogen bonds, confirming the specificity of the interaction.

Conclusions:

Our findings highlight the therapeutic potential of targeting IL-18RAcP in TNBC through modulation of IL-18/IL-18R-mediated signaling pathways. The development of scFvAPC10 offers a promising approach for novel antibody-based therapies in the treatment of TNBC.

Insights

Researchers identified a novel antibody, scFvAPC10, targeting IL-18RAcP to treat triple-negative breast cancer (TNBC). This antibody inhibits tumor growth by inducing apoptosis and blocking key signaling pathways, offering a promising new therapy for TNBC.

Area of Science:

Oncology
Immunology
Molecular Biology

Background:

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking targeted therapies.
Interleukin-18 (IL-18) signaling pathway involvement in cancer progression and poor outcomes is established.
IL-18 receptor accessory protein chain (IL-18RAcP) is crucial for IL-18 signaling initiation.

Purpose of the Study:

To investigate IL-18RAcP as a therapeutic target in TNBC.
To develop and characterize human antibodies targeting IL-18RAcP for potential TNBC treatment.

Main Methods:

Phage display screening for human single-chain variable fragment (scFv) antibodies against IL-18RAcP.
Characterization using ELISA, SPR, crystallography, qRT-PCR, MTT, Western blotting, and flow cytometry.
Functional validation in TNBC xenograft models and structural analysis of antibody-target interaction.

Main Results:

Elevated IL-18RAcP expression correlates with poor recurrence-free survival in TNBC.
Identified scFvAPC10 antibody with high affinity for IL-18RAcP.
scFvAPC10 inhibited TNBC cell proliferation in vitro, reduced tumor growth in vivo via apoptosis, and impaired NF-κB and MAPK signaling.

Conclusions:

Targeting IL-18RAcP via IL-18/IL-18R signaling modulation shows therapeutic potential for TNBC.
The developed scFvAPC10 antibody represents a promising candidate for novel antibody-based TNBC therapies.

Read full analysis

Keywords:

IL-18R accessory protein chain monoclonal antibody single-chain variable fragment triple-negative breast cancer

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