发明名称 |
DIPEPTIDYLPEPTIDASE 4 INHIBITION ENHANCES LYMPHOCYTE TRAFFICKING, IMPROVING BOTH NATURALLY OCCURRING TUMOR IMMUNITY AND IMMUNOTHERAPY |
摘要 |
The success of anti-tumor immune responses requires effector T cells to infiltrate solid tumors, a process guided by chemokines. Herein, we demonstrate that in vivo post-translational processing of chemokines by dipeptidylpeptidase 4 (DPP4, also known as CD26) limits lymphocyte migration to sites of inflammation and tumors. Inhibition of DPP4 enzymatic activity enhanced tumor rejection by preserving biologically active CXCL10, and increasing trafficking into the tumor by lymphocytes expressing the counter-receptor CXCR3. Furthermore, DPP4 inhibition improved adjuvant-based immunotherapy, adoptive T cell transfer and checkpoint blockade. These findings provide the first direct in vivo evidence for controlling lymphocyte trafficking through CXCL10 cleavage and support the use of DPP4 inhibitors for stabilizing the biologically active form of chemokines as a strategy to enhance tumor immunotherapy. |
申请公布号 |
WO2017020974(A1) |
申请公布日期 |
2017.02.09 |
申请号 |
WO2015EP79663 |
申请日期 |
2015.12.14 |
申请人 |
INSTITUT PASTEUR;INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) |
发明人 |
BARREIRA DA SILVA, Rosa;ALBERT, Matthew |
分类号 |
A61K39/00;A61K31/40;A61K31/403;A61K31/4375;A61K31/4545;A61K31/4985;A61K31/513;A61K31/522;A61K31/69;A61K35/76;A61K45/06;A61P35/00;A61P35/02;A61P35/04;A61P43/00 |
主分类号 |
A61K39/00 |
代理机构 |
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代理人 |
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地址 |
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