Related Experiment Videos
Antibody-based targeting of CD24 enhances antitumor effect of cetuximab via attenuating phosphorylation of Src/STAT3
Zhiguo Chen1, Tong Wang1, Xiaojie Tu1
1State Key Laboratory of Natural Medicines, Life Science & Technology, China Pharmaceutical University, PR China.
Abstract:
Epidermal growth factor receptor (EGFR) is a cell-surface receptor for some extracellular protein ligands relating to cancers and has been recognized as a key target for tumor therapy. Cetuximab, a chimerical monoclonal EGFR IgG1 antibody, is used for the treatment of various malignancies. However, recent clinical trials reported that the anti-tumor effect of cetuximab is still controversial. Cluster of differentiation 24 (CD24) is a tumor-associated antigen correlating with poor prognosis and regulating the activity of Src/STAT3 in multiple cancers. G7mAb was an anti-CD24 antibody derived by hybridoma technology in our previous study. To further evaluate the relationship between cetuximab and G7mAb in cancer therapy, this combination treatment was performed in vitro (A549, HT-29 and Huh-7 cells) and in vivo (xenograft mouse models). We showed that G7mAb suppressed the invasion and enhanced the anti-proliferation effect of cetuximab in A549, HT-29 and Huh-7 cells. Combination of cetuximab with G7mAb had enhanced effects on blocking the activation of signal transducer and activator of transcription 3 (STAT3) signal pathway. Furthermore, combination therapy of cetuximab with G7mAb significantly suppressed tumor developments and improved the survival rates in xenografted mice. In conclusion, G7mAb enhanced the antitumor effect of cetuximab by attenuating phosphorylation of Src/STAT3 both in vitro and in vivo. Combination of antibodies targeting EGFR or CD24 provided a potential strategy for cancer therapy.
Insights
Combining anti-CD24 antibody G7mAb with cetuximab enhances anti-cancer therapy by suppressing tumor growth and improving survival. This combination targets both EGFR and CD24, offering a promising new strategy for treating various malignancies.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Biology
Background:
- Epidermal growth factor receptor (EGFR) is a key target in cancer therapy, with cetuximab being a widely used anti-EGFR antibody.
- The clinical efficacy of cetuximab is sometimes limited, necessitating exploration of combination therapies.
- Cluster of differentiation 24 (CD24) is a tumor-associated antigen linked to poor prognosis and cancer progression via the Src/STAT3 pathway.
Purpose of the Study:
- To investigate the combined therapeutic effects of cetuximab and a novel anti-CD24 antibody (G7mAb) in vitro and in vivo.
- To determine if G7mAb enhances the anti-tumor activity of cetuximab.
- To elucidate the underlying molecular mechanisms, particularly the modulation of the Src/STAT3 signaling pathway.
Main Methods:
- In vitro studies using human cancer cell lines (A549, HT-29, Huh-7) to assess proliferation and invasion.
- In vivo studies utilizing xenograft mouse models to evaluate tumor development and survival rates.
- Analysis of the Src/STAT3 signaling pathway activation through Western blotting or similar techniques.
Main Results:
- G7mAb enhanced cetuximab's anti-proliferative effects and suppressed cancer cell invasion in vitro.
- The combination therapy significantly inhibited tumor growth and improved survival rates in mouse models.
- Combined treatment effectively attenuated the phosphorylation of Src and STAT3, key components of the signaling pathway.
Conclusions:
- G7mAb potentiates the anti-tumor efficacy of cetuximab by inhibiting the Src/STAT3 pathway.
- The combination of anti-EGFR (cetuximab) and anti-CD24 (G7mAb) antibodies presents a viable and potentially synergistic strategy for cancer treatment.
- Targeting both EGFR and CD24 offers a promising therapeutic approach for various malignancies.