Leveraging Vγ9Vδ2 T cells against prostate cancer through a VHH-based PSMA-Vδ2 bispecific T cell engager.

Vγ9Vδ2 T cells constitute a homogeneous effector T cell population that lyses tumors of different origin, including the prostate. We generated a bispecific T cell engager (bsTCE) to direct Vγ9Vδ2 T cells to PSMA prostate cancer (PCa) cells. The PSMA-Vδ2 bsTCE triggered healthy donor and PCa patient-derived Vγ9Vδ2 T cells to lyse PSMA PCa cell lines and patient-derived tumor cells while sparing normal prostate cells and enhanced Vγ9Vδ2 T cell antigen cross-presentation to CD8 T cells.

Vδ2 T-cell engagers bivalent for Vδ2-TCR binding provide anti-tumor immunity and support robust Vγ9Vδ2 T-cell expansion.

Background: Vγ9Vδ2 T-cells are antitumor immune effector cells that can detect metabolic dysregulation in cancer cells through phosphoantigen-induced conformational changes in the butyrophilin (BTN) 2A1/3A1 complex. In order to clinically exploit the anticancer properties of Vγ9Vδ2 T-cells, various approaches have been studied including phosphoantigen stimulation, agonistic BTN3A-specific antibodies, adoptive transfer of expanded Vγ9Vδ2 T-cells, and more recently bispecific antibodies. While Vγ9Vδ2 T-cells constitute a sizeable population, typically making up ~1-10% of the total T cell population, lower numbers have been observed with increasing age and in the context of disease.

Isolation and expansion of pure and functional γδ T cells.

γδ T cells are important components of the immune system due to their ability to elicit a fast and strong response against infected and transformed cells. Because they can specifically and effectively kill target cells in an MHC independent fashion, there is great interest to utilize these cells in anti-tumor therapies where antigen presentation may be hampered. Since only a small fraction of T cells in the blood or tumor tissue are γδ T cells, they require extensive expansion to allow for fundamental, preclinical and research.

A Bispecific γδ T-cell Engager Targeting EGFR Activates a Potent Vγ9Vδ2 T cell-Mediated Immune Response against EGFR-Expressing Tumors.

Vγ9Vδ2 T cells are effector cells with proven antitumor efficacy against a broad range of cancers. This study aimed to assess the antitumor activity and safety of a bispecific antibody directing Vγ9Vδ2 T cells to EGFR-expressing tumors. An EGFR-Vδ2 bispecific T-cell engager (bsTCE) was generated, and its capacity to activate Vγ9Vδ2 T cells and trigger antitumor activity was tested in multiple in vitro, in vivo, and ex vivo models.

Gamma Delta T-Cell Based Cancer Immunotherapy: Past-Present-Future.

γδ T-cells directly recognize and kill transformed cells independently of HLA-antigen presentation, which makes them a highly promising effector cell compartment for cancer immunotherapy. Novel γδ T-cell-based immunotherapies, primarily focusing on the two major γδ T-cell subtypes that infiltrate tumors ( Vδ1 and Vδ2), are being developed. The Vδ1 T-cell subset is enriched in tissues and contains both effector T-cells as well as regulatory T-cells with tumor-promoting potential.

Replicative history marks transcriptional and functional disparity in the CD8 T cell memory pool.

Clonal expansion is a core aspect of T cell immunity. However, little is known with respect to the relationship between replicative history and the formation of distinct CD8 memory T cell subgroups. To address this issue, we developed a genetic-tracing approach, termed the DivisionRecorder, that reports the extent of past proliferation of cell pools in vivo.

Enhancement of NK Cell Antitumor Effector Functions Using a Bispecific Single Domain Antibody Targeting CD16 and the Epidermal Growth Factor Receptor.

The ability to kill tumor cells while maintaining an acceptable safety profile makes Natural Killer (NK) cells promising assets for cancer therapy. Strategies to enhance the preferential accumulation and activation of NK cells in the tumor microenvironment can be expected to increase the efficacy of NK cell-based therapies. In this study, we show binding of a novel bispecific single domain antibody (VHH) to both CD16 (FcRγIII) on NK cells and the epidermal growth factor receptor (EGFR) on tumor cells of epithelial origin.

A Bispecific Single-Domain Antibody Boosts Autologous Vγ9Vδ2-T Cell Responses Toward CD1d in Chronic Lymphocytic Leukemia.

Purpose: Although considerable progress has been made with autologous T cell-based therapy in B-cell malignancies, application in chronic lymphocytic leukemia (CLL) lags behind due to disappointing response rates as well as substantial toxicity that is of particular concern in the elderly CLL population. Vγ9Vδ2-T cells form a conserved T-cell subset with strong intrinsic immunotherapeutic potential, largely because of their capacity to be triggered by phosphoantigens that can be overproduced by CLL and other malignant cells. Specific activation of Vγ9Vδ2-T cells by a bispecific antibody may improve the efficacy and toxicity of autologous T-cell-based therapy in CLL.

Targeted vaccination campaigns of teenagers after two clusters of B invasive meningococcal disease in Brittany, France, 2017.

Background: In December 2016, three cases of serogroup B invasive meningococcal disease, including two children from the same middle school (11 to 15 years old pupils), occurred in the department (administrative district) Côtes-d'Armor (Brittany, France). They were infected by a rare strain (B:P1.7-2,4:F5-9:cc162), covered by the 4CMenB vaccine (Bexsero®).

Paediatric haemolytic uraemic syndrome related to Shiga toxin-producing , an overview of 10 years of surveillance in France, 2007 to 2016.

IntroductionHaemolytic uraemic syndrome (HUS) related to Shiga toxin-producing (STEC) is the leading cause of acute renal failure in young children. In France, HUS surveillance in children aged < 15 years was implemented starting from 1996.AimWe present the results of this surveillance between 2007 and 2016.

An outbreak of leptospirosis among kayakers in Brittany, North-West France, 2016.

In September 2016, a cluster of seven kayakers with clinical symptoms of leptospirosis with onset since July 2016 was reported to French health authorities. Human and animal investigations were undertaken to describe the outbreak, identify the likely place and source of infection and implement necessary control measures. We identified 103 patients with clinical symptoms of leptospirosis between 1 June and 31 October 2016 who lived in the Ille-et-Vilaine district in Brittany.

Corrigendum: CD1d-Invariant Natural Killer T Cell-Based Cancer Immunotherapy: α-Galactosylceramide and Beyond.

[This corrects the article DOI: 10.3389/fimmu.2018.

CD1d-Invariant Natural Killer T Cell-Based Cancer Immunotherapy: α-Galactosylceramide and Beyond.

CD1d-restricted invariant natural killer T (iNKT) cells are considered an attractive target for cancer immunotherapy. Upon their activation by glycolipid antigen and/or cytokines, iNKT cells can induce direct lysis of tumor cells but can also induce an antitumor immune response their rapid production of proinflammatory cytokines that trigger the cytotoxic machinery of other components of the innate and adaptive immune system. Here, we provide an overview of various therapeutic approaches that have been evaluated or that are currently being developed and/or explored.

High Proportion of Asymptomatic Infections in an Outbreak of Hepatitis E Associated With a Spit-Roasted Piglet, France, 2013.

Background: On 11 December 2013, 3 clustered cases of hepatitis E were reported on a French coastal island. Individuals had taken part in a wedding meal that included a spit-roasted piglet. The piglet had been stuffed with a raw stuffing partly made from the liver.

Conceptualizing Forest Degradation.

Forest degradation is a global environmental issue, but its definition is problematic. Difficulties include choosing appropriate reference states, timescales, thresholds, and forest values. We dispense with many such ambiguities by interpreting forest degradation through the frame of ecological resilience, and with reference to forest dynamics.

Community Incidence of Campylobacteriosis and Nontyphoidal Salmonellosis, France, 2008-2013.

Community incidence estimates are necessary to assess the burden and impact of infections on health and to set priorities for surveillance, research, prevention, and control strategies. The current study was performed to estimate the community incidence of campylobacteriosis and nontyphoidal salmonellosis in France from the number of laboratory-confirmed cases reported to the national reference center (NRC). The probabilities of a case in the community visiting a doctor, having a stool sample requested, having a positive laboratory test, and having the case reported to the NRC were estimated using data of national surveillance systems, national hospitalization and health insurance databases, and specific surveys informing about these parameters.

Associations of age and sex with the clinical outcome and incubation period of Shiga toxin-producing Escherichia coli O104:H4 infections, 2011.

We pooled data on adults who reported diarrhea or developed life-threatening hemolytic uremic syndrome (HUS) in any of 6 closed cohorts from 4 countries (1 cohort each in Denmark, France, and Sweden and 3 in Germany) that were investigated during a large outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection in 2011. Logistic regression and Weibull regression for interval censored data were used to assess the relation of age and sex with clinical outcome and with incubation period. Information on the latter was used in a nonparametric back-projection context to estimate when adult cases reported in Germany were exposed to STEC O104:H4.

What is the incubation period for listeriosis?

Background: Listeriosis is a foodborne infection with a low incidence but a high case fatality rate. Unlike common foodborne diseases, the incubation period can be long. The first incubation periods were documented during a large listeriosis outbreak published in 1987 by Linnan and al.

Outbreak of Shiga toxin-producing Escherichia coli O104:H4 associated with organic fenugreek sprouts, France, June 2011.

Background: On 22 June 2011, 8 patients with hemolytic uremic syndrome (HUS) or bloody diarrhea were reported in France. All 8 were attendees of a community center event on 8 June near Bordeaux. Three Escherichia coli cases were confirmed by isolation of Shiga toxin-producing E.

Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany.

Background: We describe an outbreak of gastroenteritis and the hemolytic-uremic syndrome caused by Shiga-toxin-producing Escherichia coli in Germany in May, June, and July, 2011. The consumption of sprouts was identified as the most likely vehicle of infection.

Methods: We analyzed data from reports in Germany of Shiga-toxin-producing E.

Outbreak of Q fever, Florac, Southern France, Spring 2007.

Introduction: In May 2007, five patients with Q fever-like symptoms were reported in an agricultural educational center in the rural southern French town of Florac. An investigation was undertaken to identify the outbreak source and risk factors for infection, and to implement control measures.

Materials And Methods: We undertook active case finding.