Elimination of acquired resistance to PD-1 blockade via the concurrent depletion of tumour cells and immunosuppressive cells
| Autor: | Yong Lu, Ningbo Zheng, Ziyu Wang, Chengqiong Mao, Jing Fang, Xiaoyin Li, Guangxu Jin, Gang Xue, Xin Ming |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.drug_class
Programmed Cell Death 1 Receptor Cell Biomedical Engineering Medicine (miscellaneous) Bioengineering Monoclonal antibody T-Lymphocytes Regulatory law.invention Mice law Neoplasms medicine Animals 5'-Nucleotidase biology business.industry Antibodies Monoclonal Immune checkpoint Computer Science Applications Blockade Killer Cells Natural Cytolysis medicine.anatomical_structure Drug Resistance Neoplasm biology.protein Systemic administration Cancer research Suppressor Antibody business Biotechnology |
| Zdroj: | Nature Biomedical Engineering. 5:1306-1319 |
| ISSN: | 2157-846X |
| DOI: | 10.1038/s41551-021-00799-6 |
| Popis: | Antigen release resulting from the death of tumour cells induced by chemotherapies and targeted therapies can augment the antitumour responses induced by immune checkpoint blockade (ICB). However, tumours responding to ICB therapies often become resistant to them. Here we show that the specific targeting of tumour cells promotes the growth of tumour-cell variants that are resistant to ICB, and that the acquired resistance can be overcome via the concurrent depletion of tumour cells and of major types of immunosuppressive cell via a monoclonal antibody binding the enzyme CD73, which we identified as highly expressed on tumour cells and on regulatory T cells, myeloid-derived suppressor cells and tumour-associated macrophages, but not on cytolytic T lymphocytes, natural killer cells and dendritic cells. In mice with murine tumours, the systemic administration of anti-PD1 antibodies and anti-CD73 antibodies conjugated to a near-infrared dye prevented near-infrared-irradiated tumours from acquiring resistance to ICB and resulted in the eradication of advanced tumours. The elimination of immunosuppressive cells may overcome acquired resistance to ICB across a range of tumour types and combination therapies. The concurrent depletion of tumour cells and immunosuppressive cells via a monoclonal antibody targeting a common surface marker prevents tumours from acquiring resistance to therapies involving immune checkpoint blockade. |
| Databáze: | OpenAIRE |
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