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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.

Author information

1
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.
2
Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
3
Department of Pathology, Children's Hospital, Harvard Medical School, Boston, MA, USA.
4
Department of Health Sciences, University of Milano-Bicocca, Milan, Italy.
5
Department of Women and Children's Health, University of Padua, Padua, Italy.
6
Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
#
Contributed equally

Abstract

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.

KEYWORDS:

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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