Antibiotics (ATB) compromise the efficacy of immunotherapy regimens such as immune checkpoint inhibition (ICI) and CAR-T cell in patients with solid and hematological malignancies. However, prospective clinical and translational studies addressing the specific ATB types and biological mechanisms underlying their harmful effects remain deficient. Using a multi-omics approach to evaluate the local and systemic effects of ATB, we demonstrated that broad-spectrum (but not narrow) ATB adversely affect clinical outcomes across two cohorts composed of 481 (retrospective) and 145 (prospective) patients with lung, bladder, and kidney cancers (ONCOBIOTICS, NCT04567446). ATB use disrupted intestinal interkingdom microbial communities, reducing the diversity of bacterial and fungal species. Within 90 days of ATB exposure, stool metagenomics revealed a bacterial taxonomic shift with an overrepresentation of the immunosuppressive Enterocloster genus and a loss of Methanomethylophilaceae archaea. Moreover, fungal stool culturomics were more likely to be positive with a predominance of ethanol-producing fungi such as Candida spp. and C. cladosporioides. Using a dendritic cell / T cell test on isolated fungal species, patients were not defective in fungal-specific recall responses (positive in 90% versus 60% of HV), mostly Th1 and/or Th17. Blood metabolomics demonstrated that ATB significantly disrupted microbiota-derived metabolites, particularly bile acid metabolism, and the intestinal regulation of lymphocyte migration through the gut immune checkpoint mucosal addressin cell-adhesion molecule-1 (MAdCAM-1). ATB use was associated with the downregulation of the MAdCAM-1, and the recirculation of enterotropic α4β7 central memory CD4+ T cells, conventional monocytes, immature NK cells, and IgA+ CD27+ memory B cells, while promoting CD8+ T cell exhaustion. The recovery of the gut microbiota composition shift and the downregulation of MAdCAM-1 took at least 90 days after ATB stop, reinforcing the need for microbiota-centered interventions to accelerate recovery. Intriguingly, microbiota-metabolic markers such as Methanomethylophilaceaearchaea, Geotrichum candidum, and taurocholic acid identified a subset of ATB users with favorable prognosis. These findings reveal new hallmarks of ATB-associated dysbiosis that merit further investigation. Carolina Alves Costa Silva, Giacomo Vitali, Yasmine Hassani, Estelle Menu, Adele Bonato, Deborah Suissa, Lorenzo Belluomini, Anna Reni, Valerio Iebba, Roxanne Birebent, Sylvère Durand, Guillermo Hernandez, Marie Xiberras, Caroline Flament, Anne-Laure Mallard de La Varende, Simon Thomas, Milieu Intérieur Consortium, ONCOBIOTICS network, Stéphane Ranque, Pierre Edouard Fournier, Joel Doré, Guido Kroemer, Damien Drubay, Laurence Zitvogel, Lisa Derosa. Multipronged approach identifying new hallmarks of antibiotics-mediated immunosuppression in a prospective trial of cancer immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3813.
Reliable and high-throughput genotyping platforms are of immense importance for identifying and dissecting genomic regions controlling important phenotypes, supporting selection processes in breeding programs, and managing wild populations and germplasm collections. Amongst available genotyping tools, single nucleotide polymorphism arrays have been shown to be comparatively easy to use and generate highly accurate genotypic data. Single-species arrays are the most commonly used type so far; however, some multi-species arrays have been developed for closely related species that share single nucleotide polymorphism markers, exploiting inter-species cross-amplification. In this study, the suitability of a multiplexed plant-animal single nucleotide polymorphism array, including both closely and distantly related species, was explored. The performance of the single nucleotide polymorphism array across species for diverse applications, ranging from intra-species diversity assessments to parentage analysis, was assessed. Moreover, the value of genotyping pooled DNA of distantly related species on the single nucleotide polymorphism array as a technique to further reduce costs was evaluated. Single nucleotide polymorphism performance was generally high, and species-specific single nucleotide polymorphisms proved suitable for diverse applications. The multi-species single nucleotide polymorphism array approach reported here could be transferred to other species to achieve cost savings resulting from the increased throughput when several projects use the same array, and the pooling technique adds another highly promising advancement to additionally decrease genotyping costs by half.
L’allergie aux poils de cheval est de plus en plus fréquente avec le développement des sports équestres. On évoque souvent l’allergie « aux poils » de chevaux, cependant ce ne sont pas les poils qui sont responsables de cette allergie, mais des protéines sécrétées par les glandes sudoripares. Ces protéines sont des allergènes retrouvés dans l’urine, sur les squames et enfin sur les poils des chevaux. Une solution pour les cavaliers allergiques « aux poils » des chevaux serait l’utilisation de chevaux Curly. En effet, ces équidés présentent un poil frisé qui retiendraient mieux les squames que les poils raides. Bien qu’aucune étude ne l’ait encore démontré, cette particularité donne aux chevaux Curly la réputation d’être hypoallergéniques. Nous avons identifié une mutation autosomique dominante responsable de ce phénotype « poil frisé ». Cette mutation est localisée au niveau de l’un des gènes codant pour les kératines (ici KRT25). Pour aider les éleveurs à gérer au mieux ce caractère frisé du cheval Curly, un test de génotypage permettant d’identifier les animaux porteurs de cette mutation a été développé. L’utilisation de ces animaux comme reproducteurs permettra une gestion raisonnée des accouplements et le maintien du phénotype frisé.
Biologics first revolutionized cancer treatment in the late 1900s with the approval of rituximab and trastuzumab, two monoclonal antibodies targeting antigens expressed on tumor cells. Another milestone was achieved in the early 2010s with the approval of antibodies targeting immune checkpoints. Nowadays, the discovery and development of new biological entities and biological therapeutic products represent a rapidly growing market in various therapeutic areas, with about 10 to 15 biologics being approved each year. We have built a premium expert ecosystem services - DRIVE-Biologics - to support and accelerate biologics drug discovery and development in oncology, immuno-oncology, and inflammatory diseases. The DRIVE-Biologics consortium provides a unique integrated solution with specialist services from strategic partners, to access market analysis, establish the ability to design, optimize, and develop novel biological entities addressing the therapeutic target of interest. DRIVE-Biologics supplies the high-level, IND-focused discipline to rigorously manage the integrated programs integrating CMC, manufacturing, regulatory affairs and clinical trial. We will present the lead optimization and multiparameter preclinical evaluation process to select and assess biological candidates for downstream development and clinical studies: -Custom cellular model development for discovery and potency analysis; -In vitro screening, target engagement, and mechanism of action elucidation with cellular models ranging from tumor cell lines, immune cells or primary patient samples; -In vivo efficacy and safety studies using refined and highly characterized syngeneic, xenogeneic, patient-derived xenograft or humanized mouse models up to non-human primates; -DMPK capabilities to develop and validate bioanalytical methods (including GLP-compliancy) such as LBA and qPCR/RT-qPCR and also assess immunogenicity; -Biodistribution and tumor specificity analysis of bioconjugated and radiolabeled biologics. Herein, we provide DRIVE-BIO optimization and preclinical evaluation process to select promising biologics and list the key parameters to be checked. We will present our recent results which highlight the importance to optimize these parameters to improve the efficacy of biologics. Citation Format: Emily Fang, Campbell Bunce, Philip Payne, Rafael Teran, Olivier Duchamp, Caroline Mignard, Francis Bichat, Fabrice Viviani. DRIVE-Biologics: All the steps from discovery to development of novel biological entities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1537.
L’élevage des poneys de sport fait souvent appel à des croisements entre poney et cheval de sport. Ces croisements se font traditionnellement de manière très intuitive. Si cette pratique de croisement améliore l’aptitude à l’obstacle, elle rend très aléatoire le respect de la hauteur maximale au garrot dont les limites sont fixées à 1,48 m non ferré et 1,49 m ferré. Au cours des dernières années, plusieurs études génétiques ont mis en évidence des gènes majeurs (QTL) significativement associés à la taille au garrot des équidés. Plus récemment, une étude Française menée dans le cadre du projet SOGEN (Génomique du Saut d’Obstacles / 2015-2018), a confirmé les QTL précédemment identifiés mais a également permis d’identifier d’autres marqueurs génétiques (SNP) très significativement associés à la taille. Parmi ces marqueurs, trois SNP, localisés sur le chromosome 3, expliquent à eux seuls une très grande partie de la taille chez les chevaux de sport. Pour chacun de ces trois SNP, des tests de génotypage par PCR quantitative à l’aide de sondes d’hydrolyse sont disponibles au laboratoire LABÉO. La maitrise des génotypes des parents mis à la reproduction devrait rendre moins aléatoire le respect de la hauteur au garrot des poneys de sport.
