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Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.

Publication ,  Journal Article
Adams, SR; Yang, HC; Savariar, EN; Aguilera, J; Crisp, JL; Jones, KA; Whitney, MA; Lippman, SM; Cohen, EEW; Tsien, RY; Advani, SJ
Published in: Nat Commun
October 4, 2016

Tumour resistance to radiotherapy remains a barrier to improving cancer patient outcomes. To overcome radioresistance, certain drugs have been found to sensitize cells to ionizing radiation (IR). In theory, more potent radiosensitizing drugs should increase tumour kill and improve patient outcomes. In practice, clinical utility of potent radiosensitizing drugs is curtailed by off-target side effects. Here we report potent anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize to tumours based on surface receptor expression. While two classes of potent anti-tubulins, auristatins and maytansinoids, indiscriminately radiosensitize tumour cells, conjugating these potent anti-tubulins to anti-ErbB antibodies restrict their radiosensitizing capacity. Of translational significance, we report that a clinically used maytansinoid ADC, ado-trastuzumab emtansine (T-DM1), with IR prolongs tumour control in target expressing HER2+ tumours but not target negative tumours. In contrast to ErbB signal inhibition, our findings establish an alternative therapeutic paradigm for ErbB-based radiosensitization using antibodies to restrict radiosensitizer delivery.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

October 4, 2016

Volume

7

Start / End Page

13019

Location

England

Related Subject Headings

  • Tubulin Modulators
  • Trastuzumab
  • Signal Transduction
  • Radiation-Sensitizing Agents
  • Radiation, Ionizing
  • Oligopeptides
  • Neoplasms
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice
 

Citation

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Adams, S. R., Yang, H. C., Savariar, E. N., Aguilera, J., Crisp, J. L., Jones, K. A., … Advani, S. J. (2016). Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize. Nat Commun, 7, 13019. https://doi.org/10.1038/ncomms13019
Adams, Stephen R., Howard C. Yang, Elamprakash N. Savariar, Joe Aguilera, Jessica L. Crisp, Karra A. Jones, Michael A. Whitney, et al. “Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.Nat Commun 7 (October 4, 2016): 13019. https://doi.org/10.1038/ncomms13019.
Adams SR, Yang HC, Savariar EN, Aguilera J, Crisp JL, Jones KA, et al. Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize. Nat Commun. 2016 Oct 4;7:13019.
Adams, Stephen R., et al. “Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize.Nat Commun, vol. 7, Oct. 2016, p. 13019. Pubmed, doi:10.1038/ncomms13019.
Adams SR, Yang HC, Savariar EN, Aguilera J, Crisp JL, Jones KA, Whitney MA, Lippman SM, Cohen EEW, Tsien RY, Advani SJ. Anti-tubulin drugs conjugated to anti-ErbB antibodies selectively radiosensitize. Nat Commun. 2016 Oct 4;7:13019.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

October 4, 2016

Volume

7

Start / End Page

13019

Location

England

Related Subject Headings

  • Tubulin Modulators
  • Trastuzumab
  • Signal Transduction
  • Radiation-Sensitizing Agents
  • Radiation, Ionizing
  • Oligopeptides
  • Neoplasms
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice