发明名称 |
SUPPRESSION OF MYELOID DERIVED SUPPRESSOR CELLS AND IMMUNE CHECKPOINT BLOCKADE |
摘要 |
Impressive responses have been observed in patients treated with checkpoint inhibitory anti-PD-1 or anti-CTLA-4 antibodies. However, immunotherapy against poorly immunogenic cancers remains a challenge. Treatment with both anti-PD-1 and anti-CTLA-4 antibodies were unable to eradicate large, modestly immunogenic CT26 tumors or metastatic 4T1 tumors. However, co-treatment with epigenetic modulating drugs and checkpoint inhibitors markedly improved treatment outcomes, curing more than 80% of them. Functional studies revealed that the primary targets of the epigenetic modulators were myeloid-derived suppressor cells (MDSCs). A PI3K-inhibitor that reduced circulating MDSCs also cured 80% of mice with metastatic 4T1 tumors when combined with immune checkpoint inhibitors. Thus, cancers resistant to immune checkpoint blockade can be cured by eliminating MDSCs. |
申请公布号 |
CA2955177(A1) |
申请公布日期 |
2016.01.21 |
申请号 |
CA20152955177 |
申请日期 |
2015.07.13 |
申请人 |
THE JOHNS HOPKINS UNIVERSITY |
发明人 |
ZHOU, SHIBIN;VOGELSTEIN, BERT;KINZLER, KENNETH W.;KIM, KIBEM |
分类号 |
A61K31/44;A61K31/706;A61K39/395;A61P35/00 |
主分类号 |
A61K31/44 |
代理机构 |
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代理人 |
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地址 |
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