Institut Pasteur

Institut National De La Sante Et De La Recherche Medicale

The Rockefeller University

Assistance Publique-hopitaux De Paris

Matthew Albert

Rosa Barreira Da Silva

Ralph M Steinman

Nina Bhardwaj

Robert Darnell

Kayo Inaba

Yoann Madec

Jeremie Decalf

Michaela Müller-Trutwin

Cécile Goujard

Stanislas Pol

Arnaud Fontanet

Mickaël J Y Ploquin

Laurence Meyer

Mostafa Mohamed

Armanda Casrouge

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.

Dipeptidylpeptidase 4 inhibition enhances lymphocyte trafficking, improving both naturally occurring tumor immunity and immunotherapy

The invention provides methods for the identification of patients capable of controlling HIV progression, as well as to the identification of an antagonist form of IP-10 associated to HIV progression control and the uses thereof for improving the immunological response of HIV patients.

Levels of CXCL10/IP-10 forms and soluble CD26/DPPIV activity as early predictive biomarkers for HIV/SIV associated mucosal inflammation and progression towards AIDS

Levels of CXCL 10/IP-10 forms and soluble CD26/DPPIV activity as early predictive biomarkers for HIV/SIV associated mucosal inflammation and progression towards AIDS

The present invention relates to methods for the treatment of infection, a disease, or a condition using CD26 (DPIV) inhibitors. The present invention also relates to an antibody that binds to the IP-10 protein and a method of monitoring the necessity for administering a CD26 inhibitor to a patient, comprising evaluating a level of sIP-10, a activity of CD26, and/or a level of CXCR3 cells in a sample.

Methods of using sIP-10, CD26 inhibitors and CXCR3 levels in a sample to assess clearance of infection, response to interferon therapy, and treating chronic infections

This invention relates to methods and compositions useful for delivering antigens to dendritic cells which are then useful for inducing antigen-specific cytotoxic T lymphocytes and T helper cells. This invention also provides assays for evaluating the activity of cytotoxic T lymphocytes. According to the invention, antigens are targeted to dendritic cells by apoptotic cells which may also be modified to express non-native antigens for presentation to the dendritic cells. The dendritic cells which are primed by the apoptotic cells are capable of processing and presenting the processed antigen and inducing cytotoxic T lymphocyte activity or may also be used in vaccine therapies.

Methods for use of apoptotic cells to deliver antigen to dendritic cells for induction or tolerization of T cells

The present invention relates to methods for evaluating and predicting clinical outcomes in patients by measuring levels of sIP-10 protein expression as well as therapies using sIP-10 and its fragments.

Methods of using sIP-10 to assess HCV clearance and/or response to interferon therapy

Growing community of inventors

Paris, France

Matthew Albert