Differentiation or immune destruction: two pathways for therapy of squamous cell carcinomas with antibodies to the epidermal growth factor receptor.

摘要: We have carried out an immunohistochemical investigation of xenografts epidermal growth factor receptor (EGFR)-overexpressing tumors that been induced to regress by treatment with rat monoclonal antibodies (mAbs) the human EGFR [ICR16 (IgG2a), ICR62 (IgG2b), and ICR64 (IgG1)]. When mice bearing HN5 squamous cell carcinoma were treated for 5 days mAb or ICR16, found be localized uniformly on tumor membranes. However, foci cells remained following smaller than ICR16 former showed a more pronounced host mononuclear infiltrate. Examination few had not regressed completely still present as static nodules 77 final anti-EGFR mAbs revealed significant levels therapeutic in nonviable areas tumors. The microscopic apparently viable did stain when only secondary antibody was used stained positive sections first antibody. This suggests loss target antigen these residual might eradicated further mAb. Furthermore, finding keratinized undergoing regression suggested undergone terminal differentiation exposure possibility supported vitro ICR62, resulted accumulation G-G1 phases cycle expression markers involucrin cytokeratin 10. no evidence apoptosis such cells. conclude which block binding EGF transforming α can inhibit EGFR-overexpressing directing benefit may obtained via immunological mechanisms IgG2b ICR62.