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%) ALKnegative 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.

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

Mastini, Cristina;Voena, Claudia;Chiarle, Roberto
Last
2017

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%) ALKnegative 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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http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=21182&path%5B%5D=67426
Anaplastic lymphoma kinase; Autoantibodies; Immunotherapy; Lung cancer;
Awad M.M.; Mastini C.; Blasco R.B.; Mologni L.; Voena C.; Mussolin L.; Mach S.L.; Adeni A.E.; Lydon C.A.; Sholl L.M.; Janne P.A.; Chiarle R.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1679049
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