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Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7

Differential activities of Nav1.7-targeting monoclonal antibodies

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Abstract

The voltage-gated Na+ channel subtype Nav1.7 is important for pain and itch in rodents and humans. We previously showed that a Nav1.7-targeting monoclonal antibody (SVmab) reduces Na+ currents and pain and itch responses in mice. Here, we investigated whether recombinant SVmab (rSVmab) binds to and blocks Nav1.7 similar to SVmab. ELISA tests revealed that SVmab was capable of binding to Nav1.7-expressing HEK293 cells, mouse DRG neurons, human nerve tissue, and the voltage-sensor domain II of Nav1.7. In contrast, rSVmab showed no or weak binding to Nav1.7 in these tests. Patch-clamp recordings showed that SVmab, but not rSVmab, markedly inhibited Na+ currents in Nav1.7-expressing HEK293 cells. Notably, electrical field stimulation increased the blocking activity of SVmab and rSVmab in Nav1.7-expressing HEK293 cells. SVmab was more effective than rSVmab in inhibiting paclitaxel-induced mechanical allodynia. SVmab also bound to human DRG neurons and inhibited their Na+ currents. Finally, potential reasons for the differential efficacy of SVmab and rSVmab and future directions are discussed.

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Acknowledgements

This work was supported by National Institutes of Health Grants R01NS89479, R01NS045594 and R01NS055860.

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Author notes

  1. Sangsu Bang, Jiho Yoo and Xingrui Gong have contributed equally to this work.

Authors and Affiliations

  1. Department of Anesthesiology, Duke University Medical Center, 595 LaSalle St, Durham, NC, 27710, USA

    Sangsu Bang, Di Liu, Qingjian Han, Xin Luo, Wonseok Chang, Gang Chen, Yong Ho Kim & Ru-Rong Ji

  2. Department of Biochemistry, Duke University Medical Center, 303 Research Drive, Durham, NC, 27710, USA

    Jiho Yoo & Seok-Yong Lee

  3. Pain Research Center, Department of Anesthesiology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267-0531, USA

    Xingrui Gong, Judith A. Strong & Jun-Ming Zhang

  4. Department of Anesthesiology, Shanghai Children’s Medical Center, Shanghai, 200127, China

    Xingrui Gong & Ma-Zhong Zhang

  5. Department of Physiology and Biophysics, College of Medicine, Eulji University, 143-5 Yongdu-Dong, Jung-Gu, Daejeon, 34824, Korea

    Wonseok Chang

  6. Department of Physiology, College of Medicine, Gachon University, Incheon, 21999, Korea

    Sang-Taek Im & Yong Ho Kim

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  1. Sangsu Bang
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Correspondence to Jun-Ming Zhang, Seok-Yong Lee or Ru-Rong Ji.

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Bang, S., Yoo, J., Gong, X. et al. Differential Inhibition of Nav1.7 and Neuropathic Pain by Hybridoma-Produced and Recombinant Monoclonal Antibodies that Target Nav1.7. Neurosci. Bull. 34, 22–41 (2018). https://doi.org/10.1007/s12264-018-0203-0

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