Inhibition of Immunosuppressive Tumors by Polymer‐Assisted Inductions of Immunogenic Cell Death and Multivalent PD‐L1 Crosslinking

Checkpoint blockade immunotherapies harness the host's own immune system to fight cancer, but only work against tumors infiltrated by swarms of preexisting T cells. Unfortunately, most cancers to date are immune‐deserted. Here, a polymer‐assisted combination of immunogenic chemotherapy and PD‐L...

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Bibliographic Details
Published in:Advanced functional materials 2020-03, Vol.30 (12), p.n/a
Main Authors: Li, Lian, Li, Yachao, Yang, Chieh‐Hsiang, Radford, D. Christopher, Wang, Jiawei, Janát‐Amsbury, Margit, Kopeček, Jindřich, Yang, Jiyuan
Format: Article
Language:English
Subjects:
Antibodies
Apoptosis
Cancer
Cell death
checkpoint blockade immunotherapy
Chemotherapy
Crosslinking
Degradation
HPMA polymer
Immune system
immunogenic cell death
immunosuppressive tumor
Immunotherapy
Lymphocytes
Materials science
PD‐L1 crosslinking
Polymers
Priming
Tumors
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Summary:Checkpoint blockade immunotherapies harness the host's own immune system to fight cancer, but only work against tumors infiltrated by swarms of preexisting T cells. Unfortunately, most cancers to date are immune‐deserted. Here, a polymer‐assisted combination of immunogenic chemotherapy and PD‐L1 degradation is reported for efficacious treatment in originally nonimmunogenic cancer. “Priming” tumors with backbone‐degradable polymer‐epirubicin conjugates elicits immunogenic cell death and fosters tumor‐specific CD8+ T cell response. Sequential treatment with a multivalent polymer‐peptide antagonist to PD‐L1 overcomes adaptive PD‐L1 enrichment following chemotherapy, biases the recycling of PD‐L1 to lysosome degradation via surface receptor crosslinking, and produces prolonged elimination of PD‐L1 rather than the transient blocking afforded by standard anti‐PD‐L1 antibodies. Together, these findings establish the polymer‐facilitated tumor targeting of immunogenic drugs and surface crosslinking of PD‐L1 as a potential new therapeutic strategy to propagate long‐term antitumor immunity, which might broaden the application of immunotherapy to immunosuppressive cancers. Polymer‐enhanced induction of immunogenic cell death and multivalent PD‐L1 crosslinking is established as a potential new therapeutic strategy to propagate long‐term antitumor immunity, which might broaden the application of immunotherapy to immunosuppressive cancers.
ISSN:1616-301X
1616-3028
DOI:10.1002/adfm.201908961