Supplementary Materials

Supplementary Material for:

Extended release of perioperative immunotherapy prevents tumor recurrence and eliminates metastases

Chun Gwon Park, Christina A. Hartl, Daniela Schmid, Ellese M. Carmona, Hye-Jung Kim, Michael S. Goldberg*

*Corresponding author. Email: michael_goldberg1{at}dfci.harvard.edu

Published 21 March 2018, Sci. Transl. Med. 10, eaar1916 (2018)
DOI: 10.1126/scitranslmed.aar1916

This PDF file includes:

  • Fig. S1. A hydrogel composed of cross-linked hyaluronic acid is stable but biodegradable in vivo.
  • Fig. S2. The hydrogel scaffold extends the release of biologics and small molecules in vitro.
  • Fig. S3. The hydrogel scaffold extends the local release of biologics and small molecules in vivo.
  • Fig. S4. The activity of a biologic released from the hydrogel is preserved completely.
  • Fig. S5. Multiple systemic administrations of R848 fail to confer survival benefit and are less well tolerated than R848 released from a hydrogel.
  • Fig. S6. STING-RR confers superior efficacy to 2′3′-cGAMP upon extended release from a hydrogel in the perioperative setting.
  • Fig. S7. IVIS imaging confirms that STING-RR must be released from a hydrogel to protect against tumor recurrence and eliminate metastases.
  • Fig. S8. Efficacy of STING-RR loaded in a hydrogel is retained after storage for 1 week at 4°C.
  • Fig. S9. Intraoperative placement of the immunotherapy-loaded hydrogel into the tumor resection site is required for therapeutic benefit.
  • Fig. S10. Extended local release of combination immune checkpoint blockade confers limited survival benefit.
  • Fig. S11. Flow cytometric analysis confirms that NK cells, CD8+ T cells, and CD4+ T cells are depleted after administration of appropriate antibodies.
  • Fig. S12. Extended local release of STING-RR increases the number of activated innate immune cells.
  • Fig. S13. Extended local release of R848 increases the numbers of several leukocyte subsets in the lung.
  • Fig. S14. Increased concentrations of cytokines are observed in plasma collected at various time points after surgery.
  • Fig. S15. Induction of an adaptive antitumor memory response is confirmed by rejection of 4T1-Luc2 cells inoculated as rechallenge.
  • Fig. S16. Extended local release of agonists of innate immunity does not alter the composition of the blood.
  • Fig. S17. Extended local release of agonists of innate immunity is safe.
  • Fig. S18. Extended local release of agonists of innate immunity is well tolerated.
  • Fig. S19. The response of parental 4T1 cells to R848 released locally from a hydrogel is similar to that of 4T1 cells expressing Luc2.
  • Fig. S20. Localized release of perioperative immunotherapy is efficacious in the B16-BL6 model of spontaneous metastasis.
  • Fig. S21. Extended release of R848 from a scaffold derived from alginate confers survival benefit.
  • Table S1. Quantitation and statistics for a panel of cytokines measured in plasma recovered 3 and 14 days after surgery.
  • Table S2. A table of the antibodies used for flow cytometry experiments.

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