14 Feb Genetic Variants Alter Monoclonal Antibody Effects
MedicalResearch.com Interview with:
Jun-ichi Nishimura, M.D., Ph.D.
Assistant Professor Department of Hematology and Oncology
Osaka University Graduate School of Medicine
C9, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
MedicalResearch.com: What are the main findings of the study?
Dr. Nishimura: Our major findings are a C5 mutation (c.2654G→A) in Japanese patients with PNH prevents binding and blockade by eculizumab, a humanized monoclonal antibody that targets complement protein C5 and inhibits terminal complement–mediated hemolysis associated with PNH, while retaining the functional capacity of the mutant C5 to cause hemolysis.
MedicalResearch.com: Were any of the findings unexpected?
Dr. Nishimura: Yes, one patient with a poor response to eculizumab was referred to us from Argentina. Although the known C5 polymorphism (c.2654G→A) was not identified in this patient, a new mutation (c.2653C→T) was detected in the base next to the known polymorphism, suggesting the importance of this site in C5 recognition by eculizumab.
MedicalResearch.com: What should clinicians and patients take away from your report?
Dr. Nishimura: Today’s take home messages are that the polymorphism in the target protein might be important to consider in patients with a poor response to the antibody-based treatments for various diseases.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. Nishimura: We will need to verify the distribution of these variants, especially among Asian, South American, Middle Eastern, and African countries.
Citation:
Genetic Variants in C5 and Poor Response to Eculizumab
N Engl J Med 2014; 370:632-639
February 13, 2014DOI: 10.1056/NEJMoa1311084
Last Updated on February 14, 2014 by Marie Benz MD FAAD