Anti-ALK Antibodies in Patients with ALK-Positive Malignancies Not Expressing NPM-ALK

Christine Damm-Welk; Faraz Siddiqi; Matthias Fischer; Barbara Hero; Vignesh Narayanan; David Ross Camidge; Michael Harris; Amos Burke; Thomas Lehrnbecher; Karen Pulford; Ilske Oschlies; Reiner Siebert; Suzanne Turner; Wilhelm Woessmann

doi:10.7150/jca.15238

Anti-ALK Antibodies in Patients with ALK-Positive Malignancies Not Expressing NPM-ALK

J Cancer. 2016 Jun 30;7(11):1383-7. doi: 10.7150/jca.15238. eCollection 2016.

Authors

Affiliations

¹ 1. NHL-BFM Study Centre and Department of Paediatric Haematology and Oncology, Justus-Liebig-University, Giessen, Germany.
² 2. Department of Pathology, University of Cambridge, Cambridge UK.
³ 3. Department of Paediatric Haematology and Oncology University of Cologne, Germany; 4. Centre for Molecular Medicine Cologne, Medical Faculty, University of Cologne, Germany; 5. Max Planck Institute for Metabolism Research, Cologne, Germany.
⁴ 3. Department of Paediatric Haematology and Oncology University of Cologne, Germany.
⁵ 6. University of Colorado Cancer Centre, Aurora, Colorado, USA.
⁶ 7. Department of Paediatric Oncology, Addenbrooke's Hospital, Cambridge, UK.
⁷ 8. Department of Paediatric Haematology and Oncology, Goethe University, Frankfurt, Germany.
⁸ 9. Nuffield Division of Clinical Laboratory Sciences, University of Oxford, Oxford, UK.
⁹ 10. Department of Pathology, Christian-Albrechts-University, Kiel, Germany.
¹⁰ 11. Institute of Human Genetics, Christian-Albrechts-University and University Hospital Schleswig Holstein, Campus Kiel, Kiel Germany.

Abstract

Patients with Nucleophosmin (NPM)- Anaplastic Lymphoma Kinase (ALK) fusion positive Anaplastic Large Cell Lymphoma produce autoantibodies against ALK indicative of an immune response against epitopes of the chimeric fusion protein. We asked whether ALK-expression in other malignancies induces specific antibodies. Antibodies against ALK were detected in sera of one of 50 analysed ALK-expressing neuroblastoma patients, 13 of 21 ALK positive non-small cell lung carcinoma (NSCLC) patients, 13 of 22 ALK translocation-positive, but NPM-ALK-negative lymphoma patients and one of one ALK-positive rhabdomyosarcoma patient, but not in 20 healthy adults. These data suggest that boosting a pre-existent anti-ALK immune response may be more feasible for patients with ALK-positive NSCLC, lymphomas and rhabdomyosarcomas than for tumours expressing wild-type ALK.

Keywords: ALK-antibody titre; NSCLC; lymphoma; neuroblastoma.