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.

Awad, M., Mastini, C., Blasco, R., Mologni, L., Voena, C., Mussolin, L., et al. (2017). Epitope mapping of spontaneous autoantibodies to anaplastic lymphoma kinase (ALK) in non-small cell lung cancer. ONCOTARGET, 8(54), 92265-92274 [10.18632/oncotarget.21182].

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

Mastini, Cristina;Mologni, Luca;
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.
Articolo in rivista - Articolo scientifico
Anaplastic lymphoma kinase; Autoantibodies; Immunotherapy; Lung cancer; Oncology
English
2017
8
54
92265
92274
open
Awad, M., Mastini, C., Blasco, R., Mologni, L., Voena, C., Mussolin, L., et al. (2017). Epitope mapping of spontaneous autoantibodies to anaplastic lymphoma kinase (ALK) in non-small cell lung cancer. ONCOTARGET, 8(54), 92265-92274 [10.18632/oncotarget.21182].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/213645
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