The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
May. 11, 2021

Filed:

Dec. 14, 2015
Applicants:

Institut Pasteur, Paris, FR;

Institut National DE LA Sante ET DE LA Recherche Medicale (Inserm), Paris, FR;

Inventors:

Rosa Barreira Da Silva, San Francisco, CA (US);

Matthew Albert, Paris, FR;

Attorney:
Primary Examiner:
Assistant Examiner:
Int. Cl.
CPC ...
A61K 31/4985 (2006.01); A61K 31/513 (2006.01); A61K 31/522 (2006.01); A61K 35/17 (2015.01); A61K 31/4545 (2006.01); A61K 31/40 (2006.01); A61K 45/06 (2006.01); A61K 39/00 (2006.01); A61P 35/00 (2006.01); A61K 31/403 (2006.01); A61K 31/69 (2006.01); A61K 31/4375 (2006.01); A61K 47/68 (2017.01);
U.S. Cl.
CPC ...
A61K 31/4985 (2013.01); A61K 31/40 (2013.01); A61K 31/4545 (2013.01); A61K 31/513 (2013.01); A61K 31/522 (2013.01); A61K 35/17 (2013.01); A61K 39/001129 (2018.08); A61K 45/06 (2013.01); A61P 35/00 (2018.01); A61K 31/403 (2013.01); A61K 31/4375 (2013.01); A61K 31/69 (2013.01); A61K 39/0011 (2013.01); A61K 39/00117 (2018.08); A61K 39/00119 (2018.08); A61K 39/001104 (2018.08); A61K 39/001106 (2018.08); A61K 39/001112 (2018.08); A61K 39/001124 (2018.08); A61K 39/001126 (2018.08); A61K 39/001135 (2018.08); A61K 39/001151 (2018.08); A61K 39/001156 (2018.08); A61K 39/001157 (2018.08); A61K 39/001171 (2018.08); A61K 39/001181 (2018.08); A61K 39/001182 (2018.08); A61K 39/001186 (2018.08); A61K 39/001188 (2018.08); A61K 39/001191 (2018.08); A61K 39/001192 (2018.08); A61K 39/001193 (2018.08); A61K 39/001194 (2018.08); A61K 39/001195 (2018.08); A61K 47/6803 (2017.08); A61K 2039/55561 (2013.01); A61K 2300/00 (2013.01);
Abstract

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.


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