Blocking Antibodies Targeting the CD39/CD73 Immunosuppressive Pathway Unleash Immune Responses in Combination Cancer Therapies

Publication date: 21 May 2019Source: Cell Reports, Volume 27, Issue 8Author(s): Ivan Perrot, Henri-Alexandre Michaud, Marc Giraudon-Paoli, Séverine Augier, Aurélie Docquier, Laurent Gros, Rachel Courtois, Cécile Déjou, Diana Jecko, Ondine Becquart, Hélène Rispaud-Blanc, Laurent Gauthier, Benjamin Rossi, Stéphanie Chanteux, Nicolas Gourdin, Beatrice Amigues, Alain Roussel, Armand Bensussan, Jean-François Eliaou, Jérémy BastidSummaryImmune 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-CD...
Source: Cell Reports - Category: Cytology Source Type: research

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Cancer therapy is a double-edged sword, as surgery and chemotherapy can induce an inflammatory/immunosuppressive injury response that promotes dormancy escape and tumor recurrence. We hypothesized that these events could be altered by early blockade of the inflammatory cascade and/or by accelerating the resolution of inflammation. Preoperative, but not postoperative, administration of the nonsteroidal antiinflammatory drug ketorolac and/or resolvins, a family of specialized proresolving autacoid mediators, eliminated micrometastases in multiple tumor-resection models, resulting in long-term survival. Ketorolac unleashed an...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Conclusions: Due to the complexity of the behavior and biology of cells, scientists' primary focus should be on detection and elimination of sources of inflammation. Antiparasitic medications, and also antiviral, antibiotic, and antifungal medications should be thought of as underrecognized, underappreciated, and forgotten medications that can be part of cancer therapy. The information offered in this review suggests scientists should think of cancer not only as a metabolic disease but also as a metabolic parasite and should consider using antiparasitic medications under a new understanding of the role of inflammation, inf...
Source: Alternative Therapies in Health and Medicine - Category: Complementary Medicine Authors: Tags: Altern Ther Health Med Source Type: research
This study demonstrates the potential of structural systems pharmacol ogy in designing polypharmacology for precision medicine. It may facilitate transforming the conventional one-drug-one-gene-one-disease drug discovery process and single-indication polypharmacology approach into a new one-drug-multi-target-multi-indication paradigm for complex diseases.
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research
In this study, a pH ‐sensitive graphene oxide‐l‐arginine nanogel was synthesized to carry and release 5‐fluorouracil. Optimized conditions using statistical analysis, based on the maximum relative viscosity of nanogel, were evaluated: 5.489 for the concentration ofl‐arginine and 2.404 for pH. The prepared nanogels were characterized using scanning electron microscope and transmission electron microscope images and Fourier‐transform infrared spectroscopic analysis. Cytotoxicity was assessed using the sulforhodamine B (SRB) assay on MCF‐7 breast cancer cel ls. The fluorouracil release was measured by the dialys...
Source: Biotechnology and Applied Biochemistry - Category: Biochemistry Authors: Tags: Original Article Source Type: research
Authors: Gong X, Zheng Y, He G, Chen K, Zeng X, Chen Z Abstract With high morbidity and death rates, liver cancer has become one of the most common cancers in the world. But, most chemotherapeutic anticancer drugs have high toxicity as well as low specificity. To improve the treatment modalities and enhance the therapeutic effect of liver cancer, a brand new liver-targeting nanoparticle (NP), Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid (5 F)-loaded cholic acid (CA)-functionalized star-shaped poly (lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG)-lactobionic acid (LA) (5 F-loaded CA-PL...
Source: Drug Delivery - Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research
In this study, analysis of antioxidant defense was performed on the blood samples from 184 "aged" individuals aged 65-90+ years, and compared to the blood samples of 37 individuals just about at the beginning of aging, aged 55-59 years. Statistically significant decreases of Zn,Cu-superoxide dismutase (SOD-1), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were observed in elderly people in comparison with the control group. Moreover, an inverse correlation between the activities of SOD-1, CAT, and GSH-Px and the age of the examined persons was found. No age-related changes in glutathione reductas...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Publication date: Available online 15 June 2019Source: Microbes and InfectionAuthor(s): Moona Miettinen, Madhukar Vedantham, Arto T. PulliainenAbstractProtein ADP-ribosylation is a reversible post-translational modification, which alters protein activity, localization, interactome or stability, leading to perturbation of cell signaling. This review summarizes the emerging data indicating that host cell ADP-ribosylating enzymes, poly(ADP-ribose) polymerases (PARPs), influence the course of a bacterial infection, in parallel to ADP-ribosylating bacterial toxins. Host cell PARP targeting could be an efficient therapeutic appr...
Source: Microbes and Infection - Category: Infectious Diseases Source Type: research
Publication date: Available online 15 June 2019Source: Process BiochemistryAuthor(s): R. Prabhu, M. Ashik Mohammed, R. Anjali, G. Archunan, N.M. Prabhu, A. Pugazhendhi, N. SuganthyAbstractZeolitic imidazole frame work, a special class of porous crystalline material with tunable pore size has emerged as a promising candidate for biomedical applications. The present work enlightens the fabrication of methyl gallate encapsulated ZIF-L (MG@ZIF-L) by utilizing red seaweed Gracilaria debilis and evaluating its anticancer potential against lung cancer cell lines A549. The material structure and physicochemical behaviors were syst...
Source: Process Biochemistry - Category: Biochemistry Source Type: research
Publication date: 15 June 2019Source: New Scientist, Volume 242, Issue 3234Author(s): Donna Lu
Source: New Scientist - Category: Science Source Type: research
Publication date: Available online 15 June 2019Source: Journal of Photochemistry and Photobiology B: BiologyAuthor(s): Tianyu Yu, Lingling Tong, Yu Ao, Genmao Zhang, Yunpeng Liu, Hejia ZhangAbstractIn the search for developing a biomedicine based nanomaterial for therapeutic applications, here we described a new benign development of Photo-triggered Gold nanodots capped mesoporous silica nanoparticles Au@MSNs loaded with capsaicin (Cap) for photothermal therapy of cancer cells. Electron microscopic techniques (SEM and TEM) studies depict the anisotropic shape of Cap-Au@MSNs with mean size ≈110 nm. The successful am...
Source: Journal of Photochemistry and Photobiology B: Biology - Category: Speech-Language Pathology Source Type: research
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