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Published on: June 14, 2021
Cetuximab promotes immunotoxicity against rhabdomyosarcoma in vitro
Delia Herrmann1, Guido Seitz, Steven W Warmann
1Department of Pediatric Surgery, University Clinic Tübingen, Germany.
Abstract:
Multidrug resistance is a common problem in the treatment of childhood rhabdomyosarcoma (RMS). Therefore, novel treatment regimes such as immunotherapy have to be evaluated. The aim of this study was to detect possible targets on RMS cells and to investigate whether corresponding humanized antibodies could be used to treat RMS. Screening for potential targets common for different subtypes of RMS was carried out with Affymetrix mRNA expression arrays on 12 primary RMS samples. Subsequent pathway analysis revealed the epidermal growth factor receptor (EGFR) as a potential target for antibody therapy. Expression of EGFR and binding of its specific antibody Cetuximab to embryonal RMS cell lines RD and A-204 and alveolar RMS Rh30 were monitored by flow cytometry. Cetuximab activity was quantified by proliferation assay on RMS cells, and by antibody dependent cellular cytotoxicity assay with peripheral blood mononuclear cells (PBMCs). Gene expression analysis revealed a high expression of EGFR in all embryonal RMS compared with alveolar RMS. The EGFR specific antibody, Cetuximab binds to Rh30 and to RD but not to A-204 cells. Proliferation of these cells was influenced neither by Cetuximab nor by the growth factor EGF. However, cell dependent cytotoxicity of PBMCs to RMS cells such as Rh30 and RD was enhanced specifically by Cetuximab. These promising Cetuximab effects justify analysis under in vivo conditions using suitable models.
Insights
Novel immunotherapy targeting the epidermal growth factor receptor (EGFR) shows promise for childhood rhabdomyosarcoma (RMS). Cetuximab antibody enhanced immune cell attacks on RMS cells, suggesting potential for new treatment strategies.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Multidrug resistance complicates childhood rhabdomyosarcoma (RMS) treatment.
- Immunotherapy presents a potential avenue for novel RMS treatment strategies.
Purpose of the Study:
- To identify potential therapeutic targets on RMS cells.
- To evaluate the efficacy of humanized antibodies against identified targets for RMS treatment.
Main Methods:
- Affymetrix mRNA expression arrays were used to screen 12 primary RMS samples for common targets.
- Pathway analysis identified the epidermal growth factor receptor (EGFR).
- Flow cytometry, proliferation assays, and antibody-dependent cellular cytotoxicity (ADCC) assays were performed using Cetuximab.
Main Results:
- High EGFR expression was observed in embryonal RMS compared to alveolar RMS.
- Cetuximab bound to Rh30 and RD cell lines but not A-204.
- Cetuximab did not affect RMS cell proliferation but enhanced ADCC by PBMCs against Rh30 and RD cells.
Conclusions:
- EGFR is a potential target for antibody therapy in RMS, particularly embryonal subtypes.
- Cetuximab demonstrates potential in enhancing immune-mediated killing of RMS cells.
- Further in vivo studies are warranted to validate Cetuximab's therapeutic efficacy in RMS models.