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Updated: Jun 5, 2025
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Novel affibody molecules targeting the AXL extracellular structural domain for molecular imaging and targeted therapy
HuiHui Zhang1, Maolin Zheng1, YiQi Cai2
1Institute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, 325035, Zhejiang, People's Republic of China.
Abstract:
Gastric cancer (GC) has a poor prognosis and high mortality because it is often diagnosed at an advanced stage. Targeted therapeutics are considered an important class for advanced GC treatment. However, the fewer effective therapeutic targets and the poor coverage of the GC population limit the use of GC targeted therapies. Recent research suggests that the AXL receptor tyrosine kinase (AXL) plays an vital role in the survival and proliferation of GC cells, and blocking AXL pathway may be an effective strategy for targeted therapies. On the other hand, the affibody molecule, with its small size and faster penetration of tissue, has great potential in tumor imaging and targeted therapy. In this study, we report the novel AXL-binding affibody molecules (ZAXL:239) screened by a phage-displayed peptide library. The ZAXL:239 could specifically bind and interact with AXL proteins in vitro and in vivo, as demonstrated by surface plasmon resonance, co-immunoprecipitation, immuno-fluorescence co-localization, and near infrared fluorescent imaging. In addition, ZAXL:239 affibody molecules could significantly inhibit the proliferative activity and induce apoptosis of AXL-positive GC cells by decreasing the phosphorylation levels of the PI3K/AKT1 and MEK/ERK pathway, leading to the suppression of the downstream nuclear protein c-myc. Moreover, ZAXL:239 was found to have significant anti-tumor effects in AXL-positive GC transplantation tumor nude mouse models. In brief, we provide strong evidence that the novel ZAXL:239 affibody molecules have great potential as a potent tumor-specific molecular imaging and targeted therapeutic agents for GC.
Insights
Researchers developed novel AXL-binding affibody molecules (ZAXL:239) for gastric cancer (GC). These molecules target AXL-positive GC cells, inhibiting proliferation and inducing apoptosis, showing potential for imaging and therapy.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Gastric cancer (GC) has a poor prognosis, often diagnosed at advanced stages.
- Targeted therapies are crucial for advanced GC, but effective targets and population coverage are limited.
- The AXL receptor tyrosine kinase (AXL) is implicated in GC cell survival and proliferation, presenting a potential therapeutic target.
Purpose of the Study:
- To screen and characterize novel AXL-binding affibody molecules for gastric cancer (GC) targeted therapy and imaging.
- To evaluate the efficacy of ZAXL:239 affibody molecules in inhibiting GC cell proliferation and inducing apoptosis.
- To assess the anti-tumor effects of ZAXL:239 in preclinical models of GC.
Main Methods:
- Screening of AXL-binding affibody molecules using phage-displayed peptide libraries.
- In vitro and in vivo validation of ZAXL:239 binding and interaction with AXL proteins (SPR, co-IP, IF, NIR imaging).
- Assessment of ZAXL:239 effects on GC cell proliferation, apoptosis, and signaling pathways (PI3K/AKT, MEK/ERK, c-myc).
- Evaluation of anti-tumor efficacy in AXL-positive GC xenograft mouse models.
Main Results:
- Novel AXL-binding affibody molecules, ZAXL:239, were successfully identified.
- ZAXL:239 demonstrated specific binding to AXL proteins in vitro and in vivo.
- ZAXL:239 inhibited proliferation and induced apoptosis in AXL-positive GC cells by modulating PI3K/AKT and MEK/ERK pathways.
- Significant anti-tumor effects were observed in GC xenograft models.
Conclusions:
- ZAXL:239 affibody molecules are potent and specific binders of AXL.
- These affibody molecules effectively inhibit GC cell growth and induce apoptosis.
- ZAXL:239 shows significant potential as a dual-purpose agent for molecular imaging and targeted therapy in AXL-positive GC.
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