Research Papers:

Epitope mapping of spontaneous autoantibodies to anaplastic lymphoma kinase (ALK) in non-small cell lung cancer

Mark M. Awad _, Cristina Mastini, Rafael B. Blasco, Luca Mologni, Claudia Voena, Lara Mussolin, Stacy L. Mach, Anika E. Adeni, Christine A. Lydon, Lynette M. Sholl, Pasi A. Jänne and Roberto Chiarle

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Oncotarget. 2017; 8:92265-92274. https://doi.org/10.18632/oncotarget.21182

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Mark M. Awad1,*, Cristina Mastini2,*, Rafael B. Blasco3, Luca Mologni4, Claudia Voena2, Lara Mussolin5, Stacy L. Mach1, Anika E. Adeni1, Christine A. Lydon1, Lynette M. Sholl6, Pasi A. Jänne1 and Roberto Chiarle2,3

1Lowe Center for Thoracic Oncology, Department of Medical Oncology, Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

2Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy

3Department of Pathology, Children’s Hospital, Harvard Medical School, Boston, MA, USA

4Department of Health Sciences, University of Milano-Bicocca, Milan, Italy

5Department of Women and Children’s Health, University of Padua, Padua, Italy

6Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

*These authors have contributed equally to this work

Correspondence to:

Mark M. Awad, email: [email protected]

Roberto Chiarle, email: [email protected]

Keywords: lung cancer, anaplastic lymphoma kinase, autoantibodies, immunotherapy

Received: January 31, 2017     Accepted: August 25, 2017     Published: September 23, 2017


The anaplastic lymphoma kinase (ALK) is recognized by the immune system as a tumor antigen, and preclinical evidence suggests that ALK-rearranged NSCLCs can also be successfully targeted immunologically using vaccine-based approaches. In contrast to ALK-rearranged lymphomas, the frequency and clinical significance of spontaneous ALK immune responses in patients with ALK-rearranged NSCLCs are largely unknown. We developed an enzyme-linked immunosorbent assay (ELISA) to measure anti-ALK antibody levels and mapped specific peptide epitope sequences within the ALK cytoplasmic domain in patients with non-small cell lung cancer. The ELISA method showed good correlation with ALK antibody titers measured with a standard immunocytochemical approach. Strong anti-ALK antibody responses were detected in 9 of 53 (17.0%) ALK-positive NSCLC patients and in 0 of 38 (0%) ALK-negative NSCLC patients (P<0.01), and the mean antibody levels were significantly higher in ALK-positive than in ALK-negative NSCLC patients (P=0.02). Across individual patients, autoantibodies recognized different epitopes in the ALK cytoplasmic domain, most of which clustered outside the tyrosine kinase domain. Whether the presence of high ALK autoantibody levels confers a more favorable prognosis in this patient population warrants further investigation.

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