title: Immune biomarkers of anti-EGFR monoclonal antibody therapy.
abstract: The tumor antigen (TA)-targeted monoclonal antibodies (mAb) cetuximab and panitumumab target the human epidermal growth factor receptor and have been integrated into treatment regimens for advanced squamous cell carcinoma of the head and neck (SCCHN). The therapeutic efficacy of these mAbs has been found to be enhanced when combined with radiotherapy and chemotherapy. However, clinical trials indicate that these findings are limited to fewer than 20% of treated patients. Therefore, identifying patients who are likely to benefit from these agents is crucial to improving therapeutic strategies. Interestingly, it has been noted that TA-targeted mAbs mediate their effects by contributing to cell-mediated cytotoxicity in addition to inhibition of downstream signaling pathways. Here, we describe the potential immunogenic mechanisms underlying these clinical findings, their role in the varied clinical response and identify the putative biomarkers of antitumor activity. We review potential immunological biomarkers that affect mAb therapy in SCCHN patients, the implications of these findings and how they translate to the clinical scenario, which are critical to improving patient selection and ultimately outcomes for patients undergoing therapy.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine.
authors.forename: S
authors.initials: S
authors.lastname: Trivedi
authors.affiliation: Department of Immunology, University of Pittsburgh.
authors.forename: F
authors.initials: F
authors.lastname: Concha-Benavente
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine.
authors.forename: R M
authors.initials: RM
authors.lastname: Srivastava
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine.
authors.forename: H B
authors.initials: HB
authors.lastname: Jie
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine.
authors.forename: S P
authors.initials: SP
authors.lastname: Gibson
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine.
authors.forename: N C
authors.initials: NC
authors.lastname: Schmitt
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine; Department of Immunology, University of Pittsburgh; Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, USA. Electronic address: ferrrl@upmc.edu.
authors.forename: R L
authors.initials: RL
authors.lastname: Ferris
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D000068818:Cetuximab; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008264:Macrophages / Q000276:immunology; D000077544:Panitumumab; D030361:Papillomavirus Infections; D017452:Receptors, IgG / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000276:immunology; D000077195:Squamous Cell Carcinoma of Head and Neck; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D019139:Tumor Escape / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015415:Biomarkers; D015395:Histocompatibility Antigens Class I; D017452:Receptors, IgG; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000077544:Panitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors; D000068818:Cetuximab
keywords: EGFR; head and neck cancer; immune biomarkers; monoclonal antibodies