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

Hua Wang, Alexander J. Najibi, Miguel C. Sobral, Bo Ri Seo, Jun Yong Lee, David Wu, Aileen Weiwei Li, Catia S. Verbeke and David J. Mooney ()
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Hua Wang: Harvard University
Alexander J. Najibi: Harvard University
Miguel C. Sobral: Harvard University
Bo Ri Seo: Harvard University
Jun Yong Lee: Harvard University
David Wu: Harvard University
Aileen Weiwei Li: Harvard University
Catia S. Verbeke: Harvard University
David J. Mooney: Harvard University

Nature Communications, 2020, vol. 11, issue 1, 1-14

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-19540-z

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