| Added by | Nathalie Bonnefoy |
|---|---|
| Last modified by | informatique.ircm |
| Group name | EquipeNB |
| Item Type | Journal Article |
| Title | Blocking Antibodies Targeting the CD39/CD73 Immunosuppressive Pathway Unleash Immune Responses in Combination Cancer Therapies |
| Creator | Perrot et al. |
| Author | Ivan Perrot |
| Author | Henri-Alexandre Michaud |
| Author | Marc Giraudon-Paoli |
| Author | Séverine Augier |
| Author | Aurélie Docquier |
| Author | Laurent Gros |
| Author | Rachel Courtois |
| Author | Diana Jecko |
| Author | Ondine Becquart |
| Author | Hélène Rispaud-Blanc |
| Author | Laurent Gauthier |
| Author | Benjamin Rossi |
| Author | Stéphanie Chanteux |
| Author | Nicolas Gourdin |
| Author | Beatrice Amigues |
| Author | Alain Roussel |
| Author | Armand Bensussan |
| Author | Jean-François Eliaou |
| Author | Jérémy Bastid |
| Author | François Romagné |
| Author | Yannis Morel |
| Author | Emilie Narni-Mancinelli |
| Author | Eric Vivier |
| Author | Carine Paturel |
| Author | Nathalie Bonnefoy |
| Abstract | Immune checkpoint inhibitors have revolutionized cancer treatment. However, many cancers are resistant to ICIs, and the targeting of additional inhibitory signals is crucial for limiting tumor evasion. The production of adenosine via the sequential activity of CD39 and CD73 ectoenzymes participates to the generation of an immunosuppressive tumor microenvironment. In order to disrupt the adenosine pathway, we generated two antibodies, IPH5201 and IPH5301, targeting human membrane-associated and soluble forms of CD39 and CD73, respectively, and efficiently blocking the hydrolysis of immunogenic ATP into immunosuppressive adenosine. These antibodies promoted antitumor immunity by stimulating dendritic cells and macrophages and by restoring the activation of T cells isolated from cancer patients. In a human CD39 knockin mouse preclinical model, IPH5201 increased the anti-tumor activity of the ATP-inducing chemotherapeutic drug oxaliplatin. These results support the use of anti-CD39 and anti-CD73 monoclonal antibodies and their combination with immune checkpoint inhibitors and chemotherapies in cancer. |
| Publication | Cell Reports |
| Volume | 27 |
| Issue | 8 |
| Pages | 2411-2425.e9 |
| Date | May 21, 2019 |
| Journal Abbr | Cell Rep |
| Language | eng |
| DOI | 10.1016/j.celrep.2019.04.091 |
| ISSN | 2211-1247 |
| Library Catalog | PubMed |
| Extra | PMID: 31116985 |
| Tags | adenosine pathway, cancer immunotherapies, CD39, CD73, first-last-corresponding, immunosuppression, original, premium_IRCM, therapeutic antibodies, top, tumor micro-environment |
| Date Added | 2019/05/28 - 15:37:46 |
| Date Modified | 2025/01/10 - 11:15:03 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
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