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Oncotarget. 2017 Sep 23;8(54):92265-92274. doi: 10.18632/oncotarget.21182. eCollection 2017 Nov 3.

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

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Lowe Center for Thoracic Oncology, Department of Medical Oncology, Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
Department of Pathology, Children's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Health Sciences, University of Milano-Bicocca, Milan, Italy.
Department of Women and Children's Health, University of Padua, Padua, Italy.
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Contributed equally


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.


anaplastic lymphoma kinase; autoantibodies; immunotherapy; lung cancer

Conflict of interest statement

CONFLICTS OF INTEREST Mark M. Awad: Consultant for Abbvie, Ariad, Clovis, Pfizer, Nektar, Genentech, AstraZeneca, Bristol Myers Squibb, Merck, EMD Serono. Pasi A. Jänne: Consultant for AstraZeneca, Ariad, Chugai Pharmaceuticals, Pfizer, Roche/Genentech, Merrimack Pharmaceuticals, Boehringer Ingelheim, Loxo Oncology; Sponsored research support AstraZeneca and Astellas Pharmaceuticals; Stock Ownership Gatekeeper Pharmaceuticals; Post-marketing royalties from DFCI owned intellectual property on EGFR mutations licensed to Lab Corp. Roberto Chiarle: Consultant for Minerva Biotechnologies Corporation. The remaining authors have no conflicts of interest.

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