Biomaterial-based scaffold for in situ chemo-immunotherapy to treat poorly immunogenic tumors

Nat Commun. 2020 Nov 10;11(1):5696. doi: 10.1038/s41467-020-19540-z.


Poorly immunogenic tumors, including triple negative breast cancers (TNBCs), remain resistant to current immunotherapies, due in part to the difficulty of reprogramming the highly immunosuppressive tumor microenvironment (TME). Here we show that peritumorally injected, macroporous alginate gels loaded with granulocyte-macrophage colony-stimulating factor (GM-CSF) for concentrating dendritic cells (DCs), CpG oligonucleotides, and a doxorubicin-iRGD conjugate enhance the immunogenic death of tumor cells, increase systemic tumor-specific CD8 + T cells, repolarize tumor-associated macrophages towards an inflammatory M1-like phenotype, and significantly improve antitumor efficacy against poorly immunogenic TNBCs. This system also prevents tumor recurrence after surgical resection and results in 100% metastasis-free survival upon re-challenge. This chemo-immunotherapy that concentrates DCs to present endogenous tumor antigens generated in situ may broadly serve as a facile platform to modulate the suppressive TME, and enable in situ personalized cancer vaccination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antigens, Neoplasm / metabolism
  • Biocompatible Materials / therapeutic use*
  • Biotechnology / methods
  • CD8-Positive T-Lymphocytes / immunology
  • Cancer Vaccines / therapeutic use*
  • Dendritic Cells / immunology
  • Drug Delivery Systems / methods
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Humans
  • Immunologic Factors / metabolism
  • Immunologic Factors / therapeutic use
  • Immunotherapy / methods*
  • Macrophages / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / prevention & control
  • Neoplasms / immunology
  • Neoplasms / therapy
  • Triple Negative Breast Neoplasms / immunology
  • Triple Negative Breast Neoplasms / therapy*
  • Tumor Microenvironment / immunology


  • Antigens, Neoplasm
  • Biocompatible Materials
  • Cancer Vaccines
  • Immunologic Factors
  • Granulocyte-Macrophage Colony-Stimulating Factor