Biomaterial-based scaffold for in situ chemo-immunotherapy to treat poorly immunogenic tumors
| Autor: | Jun Yong Lee, David J. Mooney, Bo Ri Seo, David M. Wu, Catia S. Verbeke, Miguel C. Sobral, Hua Wang, Aileen Weiwei Li, Alexander J. Najibi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer therapy medicine.medical_treatment General Physics and Astronomy Biocompatible Materials Triple Negative Breast Neoplasms 02 engineering and technology CD8-Positive T-Lymphocytes Biomaterials - vaccines Mice Drug Delivery Systems Neoplasms Tumor Microenvironment Medicine lcsh:Science Triple-negative breast cancer Cancer Mice Inbred BALB C Multidisciplinary 021001 nanoscience & nanotechnology Phenotype Vaccination Female Immunotherapy 0210 nano-technology Reprogramming Biotechnology Science Cancer Vaccines complex mixtures General Biochemistry Genetics and Molecular Biology Article Biomaterials 03 medical and health sciences Antigen Antigens Neoplasm Animals Humans Immunologic Factors Tumor microenvironment business.industry Macrophages Granulocyte-Macrophage Colony-Stimulating Factor General Chemistry Dendritic Cells medicine.disease Mice Inbred C57BL 030104 developmental biology Cancer research lcsh:Q Neoplasm Recurrence Local business |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-14 (2020) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. The immunosuppressive tumour microenvironment impairs immunotherapy in poorly immunogenic cancer. Here, the authors load an alginate gel with GM-CSF, CpG oligonucleotides and doxorubicin-iRGD to promote immunogenic death of tumour cells and improve immunotherapy efficacy in triple negative breast cancer models. |
| Databáze: | OpenAIRE |
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