Supplementary Materials

Supplementary Material for:

AZD9150, a next-generation antisense oligonucleotide inhibitor of STAT3 with early evidence of clinical activity in lymphoma and lung cancer

David Hong, Razelle Kurzrock,* Youngsoo Kim, Richard Woessner, Anas Younes, John Nemunaitis, Nathan Fowler, Tianyuan Zhou, Joanna Schmidt, Minji Jo, Samantha J. Lee, Mason Yamashita, Steven G. Hughes, Luis Fayad, Sarina Piha-Paul, Murali V. P. Nadella, Morvarid Mohseni, Deborah Lawson, Corinne Reimer, David C. Blakey, Xiaokun Xiao, Jeff Hsu, Alexey Revenko, Brett P. Monia, A. Robert MacLeod*

*Corresponding author. E-mail: rkurzrock{at}mail.ucsd.edu (R.K.); rmacleod{at}isisph.com (A.R.M.)

Published 18 November 2015, Sci. Transl. Med. 7, 314ra185 (2015)
DOI: 10.1126/scitranslmed.aac5272

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Activity of AZD9150 and Gen 2.0 STAT3 ASO in tumor cells in vitro determined by qRT-PCR.
  • Fig. S2. Loss of sensitivity of primary cells to ASO over time when plated in culture.
  • Fig. S3. Activity of AZD9150 and Gen 2.0 STAT3 ASO in tumor cells in vitro determined by immunoblot.
  • Fig. S4. Superior activity of AZD9150 over Gen 2.0 STAT3 MOE ASO.
  • Fig. S5. Lack of activity of STAT3 siRNAs when delivered to tumor cells by free uptake.
  • Fig. S6. A decrease in the expression of STAT3 target genes after downregulation of STAT3 by ASOs in KARPAS299 cells.
  • Fig. S7. Sensitivity of ALCL cell lines, KARPAS299 and SUP-M2, to STAT3 inhibition.
  • Fig. S8. Effect of STAT3 inhibition on cell proliferation in a variety of cell types in vitro.
  • Fig. S9. IHC of ASOs and STAT3 in A431 xenograft tumors.
  • Fig. S10. Effect of AZD9150 on the growth of A431 xenograft tumors.
  • Fig. S11. Selectivity of AZD9150 for STAT3 over STAT1 or STAT5 in lymphoma patient–derived xenografts.
  • Fig. S12. Toxicity testing of AZD9150 in animals bearing SUP-M2 tumors.
  • Fig. S13. Antitumor activity of AZD9150 in SUP-M2 dissemination model.
  • Fig. S14. Toxicity testing of AZD9150 in animals bearing patient–derived lymphoma xenografts.
  • Fig. S15. Pharmacokinetic data for AZD9150.
  • Fig. S16. Changes in platelet count.
  • Fig. S17. Clinical antitumor activity of AZD9150.
  • Table S1. Quantification of ASO accumulation in A431 tumor.
  • Table S2. AZD9150 phase 1 patient demographics.
  • Table S3. Adverse events greater than 5% for all doses.
  • Table S4. Previous treatment regimens of DLBCL patients 1001 and 2012.
  • Table S5. List of primer and probe sequences used for qRT-PCR.
  • Table S6. Changes in tumor volume during the course of ASO treatment.
  • References (5860)

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