EGFR e Inmunoterapia

Immune biomarkers of anti-EGFR monoclonal antibody therapy.

Trivedi S¹, Concha-Benavente F², Srivastava RM¹, Jie HB¹, Gibson SP¹, Schmitt NC¹, Ferris RL³.

¹Department of Otolaryngology, University of Pittsburgh School of Medicine.
²Department of Immunology, University of Pittsburgh.
³Department of Otolaryngology, University of Pittsburgh School of Medicine Department of Immunology, University of Pittsburgh Cancer Immunology Program, University of Pittsburgh Cancer Institute, Pittsburgh, USA ferrrl@upmc.edu.

 

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.
© The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

KEYWORDS:

EGFR; head and neck cancer; immune biomarkers; monoclonal antibodies

Ann Oncol. 2015 Jan;26(1):40-7. doi: 10.1093/annonc/mdu156. Epub 2014 Jul 4.

http://annonc.oxfordjournals.org/content/26/1/40.long

Md. PhD. Fernando Concha. Ex-miembro del GII