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Melanoma: HELP
Articles by Julie Charles
Based on 15 articles published since 2008
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Between 2008 and 2019, J. Charles wrote the following 15 articles about Melanoma.
 
+ Citations + Abstracts
1 Guideline [Treatment of patients with inoperable stage III or stage IV melanoma. Société française de dermatologie]. 2018

Guillot, B / Charles, J / Jeudy, G / Cupissol, D / Dupuy, A / Dutriaux, C / Gangloff, D / Magne, N / Mirabel, X / M'Sadek, A / Pracht, M / Sichel, C / Do Outeiro, G. ·Département de dermatologie, hôpital Saint-Éloi, CHU de Montpellier, 34295 Montpellier, France. Electronic address: b-guillot@chu-montpellier.fr. · CHU de Grenoble, 38700 Grenoble, France. · CHU de Dijon, 21000 Dijon, France. · Institut du Cancer de Montpellier, 34298 Montpellier, France. · CHU de Rennes, 35000 Rennes, France. · CHU de Bordeaux, 33000 Bordeaux, France. · Institut universitaire du cancer de Toulouse, 31100 Toulouse, France. · Institut de cancérologie de la Loire, 42270 Saint-Priest-en-Jarez, France. · Centre Oscar-Lambret, 59000 Lille, France. · Centre Eugène-Marquis, 35000 Rennes, France. · 13470 Carnoux en Provence, France. · Institut national du cancer de Boulogne-Billancourt, 92100 Boulogne-Billancourt, France. ·Ann Dermatol Venereol · Pubmed #29703640.

ABSTRACT: -- No abstract --

2 Review Plasma Circulating Tumor DNA Levels for the Monitoring of Melanoma Patients: Landscape of Available Technologies and Clinical Applications. 2017

Busser, Benoit / Lupo, Julien / Sancey, Lucie / Mouret, Stéphane / Faure, Patrice / Plumas, Joel / Chaperot, Laurence / Leccia, Marie Thérèse / Coll, Jean Luc / Hurbin, Amandine / Hainaut, Pierre / Charles, Julie. ·Biochemistry Pharmacology and Toxicology Department, Grenoble University Hospital, Grenoble, France. · Institute for Advanced Biosciences, UGA/INSERM U1209/CNRS UMR5309, Grenoble, France. · Virology Laboratory, Grenoble University Hospital, Grenoble, France. · Institut de Biologie Structurale, CEA-CNRS UMR 5075/UGA, Grenoble, France. · Dermatology Unit, Grenoble University Hospital, Grenoble, France. · UGA, Laboratory of Hypoxy Physiopathology Study, INSERM U1042, Grenoble, France. · EFS Rhone-Alpes-Auvergne, Grenoble, France. ·Biomed Res Int · Pubmed #28484715.

ABSTRACT: Melanoma is a cutaneous cancer with an increasing worldwide prevalence and high mortality due to unresectable or metastatic stages. Mutations in

3 Review [Mechanisms of resistance to anti-BRAF treatments]. 2014

Charles, J / Martel, C / de Fraipont, F / Leccia, M-T / Robert, C / Busser, B. ·Centre de recherche Inserm/UJF U823, institut Albert-Bonniot, BP 170, 38042 Grenoble cedex 9, France; Dermatologie, CHU de Grenoble, CS 10217, 38043 Grenoble cedex 9, France. · Centre de recherche Inserm/UJF U823, institut Albert-Bonniot, BP 170, 38042 Grenoble cedex 9, France. · Unité médicale de biochimie des cancers et biothérapies, institut de biologie et pathologie, CHU de Grenoble, CS 10217, 38043 Grenoble cedex 09, France. · Inserm U981, Institut Gustave-Roussy, 114, rue Edouard-Vaillant, 94805 Villejuif-Paris-Sud, France. · Centre de recherche Inserm/UJF U823, institut Albert-Bonniot, BP 170, 38042 Grenoble cedex 9, France. Electronic address: bbusser@chu-grenoble.fr. ·Ann Dermatol Venereol · Pubmed #25442471.

ABSTRACT: CONTEXT: In patients with melanoma positive for the BRAF V600 mutation, clinical response to specific BRAF inhibitors is usually rapid and striking, with significant benefits in terms of progression-free survival and overall survival. However, resistance to treatment almost invariably arises, typically within a median timeframe of 6 months. Indeed, very few patients exhibit long-lasting response to these targeted therapies. AIMS: It is essential to better understand the mechanisms of resistance to targeted anti-BRAF therapies in order to increase both response rates and the duration of clinical response to treatment. This literature review describes the signaling pathways involving BRAF and presents recent data from clinical trials with these molecules. Furthermore, we aim to describe the main resistance mechanisms linked with targeted anti-BRAF therapies. METHODS: The keywords (resistance, BRAF, melanoma, targeted therapy, vemurafenib, and dabrafenib) were used to extract relevant articles in the Medline/Pubmed database published before 31 January 2014. DISCUSSION: Improved knowledge and understanding of the mechanisms of resistance to targeted anti-BRAF therapies should enable the development of new therapeutic strategies in order to overcome such resistance and allow more significant and sustained response rates to be achieved among melanoma patients.

4 Clinical Trial Nivolumab in previously untreated melanoma without BRAF mutation. 2015

Robert, Caroline / Long, Georgina V / Brady, Benjamin / Dutriaux, Caroline / Maio, Michele / Mortier, Laurent / Hassel, Jessica C / Rutkowski, Piotr / McNeil, Catriona / Kalinka-Warzocha, Ewa / Savage, Kerry J / Hernberg, Micaela M / Lebbé, Celeste / Charles, Julie / Mihalcioiu, Catalin / Chiarion-Sileni, Vanna / Mauch, Cornelia / Cognetti, Francesco / Arance, Ana / Schmidt, Henrik / Schadendorf, Dirk / Gogas, Helen / Lundgren-Eriksson, Lotta / Horak, Christine / Sharkey, Brian / Waxman, Ian M / Atkinson, Victoria / Ascierto, Paolo A. ·The authors' affiliations are listed in the Appendix. ·N Engl J Med · Pubmed #25399552.

ABSTRACT: BACKGROUND: Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study. METHODS: We randomly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab (at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks) or dacarbazine (at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks). The primary end point was overall survival. RESULTS: At 1 year, the overall rate of survival was 72.9% (95% confidence interval [CI], 65.5 to 78.9) in the nivolumab group, as compared with 42.1% (95% CI, 33.0 to 50.9) in the dacarbazine group (hazard ratio for death, 0.42; 99.79% CI, 0.25 to 0.73; P<0.001). The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group (hazard ratio for death or progression of disease, 0.43; 95% CI, 0.34 to 0.56; P<0.001). The objective response rate was 40.0% (95% CI, 33.3 to 47.0) in the nivolumab group versus 13.9% (95% CI, 9.5 to 19.4) in the dacarbazine group (odds ratio, 4.06; P<0.001). The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups, including subgroups defined by status regarding the programmed death ligand 1 (PD-L1). Common adverse events associated with nivolumab included fatigue, pruritus, and nausea. Drug-related adverse events of grade 3 or 4 occurred in 11.7% of the patients treated with nivolumab and 17.6% of those treated with dacarbazine. CONCLUSIONS: Nivolumab was associated with significant improvements in overall survival and progression-free survival, as compared with dacarbazine, among previously untreated patients who had metastatic melanoma without a BRAF mutation. (Funded by Bristol-Myers Squibb; CheckMate 066 ClinicalTrials.gov number, NCT01721772.).

5 Article The avidity of tumor-specific T cells amplified by a plasmacytoid dendritic cell-based assay can predict the clinical evolution of melanoma patients. 2018

Charles, Julie / Chaperot, Laurence / Revol, Bruno / Baudin, Marine / Mouret, Stephane / Hamon, Agnes / Leccia, Marie-Therese / Plumas, Joel / Aspord, Caroline. ·University Grenoble Alpes, Grenoble, France. · Immunobiology& Immunotherapy of Chronic Diseases, U1209, INSERM, La Tronche, France. · Dermatology, Pôle Pluridisciplinaire de Médecine, CHU Grenoble Alpes, Grenoble, France. · R&D Laboratory, Etablissement Français du Sang Rhone-Alpes, La Tronche, France. · Pharmacovigilance Department, CHU Grenoble Alpes, Grenoble, France. · Laboratoire Jean Kuntzmann, Universite Grenoble Alpes, Grenoble, France. ·Pigment Cell Melanoma Res · Pubmed #28741900.

ABSTRACT: The advent of immune checkpoint blockers and targeted therapies has changed the outcome of melanoma. However, many patients experience relapses, emphasizing the need for predictive and prognostic biomarkers. We developed a strategy based on plasmacytoid dendritic cells (pDCs) loaded with melanoma tumor antigens that allows eliciting highly efficient antitumor T-cell responses. We used it to investigate antitumor T-cell functionality in peripheral blood mononuclear cells and tumor-infiltrating lymphocytes from melanoma patients. The pDCs elicited tumor-specific T cells in different proportions and displaying diverse functional features, dependent upon the stage of the disease, but independent of the histological parameters at diagnosis. Strikingly, the avidity of the MelA-specific T cells triggered by the pDCs was found to predict patient relapse time and overall survival. Our findings highlighted unexplored aspects of antitumor T-cell responsiveness in melanoma, and revealed for the first time the structural avidity of tumor-specific T cells as a crucial feature for predicting clinical evolution.

6 Article Efficacy and Safety of Nivolumab Alone or in Combination With Ipilimumab in Patients With Mucosal Melanoma: A Pooled Analysis. 2017

D'Angelo, Sandra P / Larkin, James / Sosman, Jeffrey A / Lebbé, Celeste / Brady, Benjamin / Neyns, Bart / Schmidt, Henrik / Hassel, Jessica C / Hodi, F Stephen / Lorigan, Paul / Savage, Kerry J / Miller, Wilson H / Mohr, Peter / Marquez-Rodas, Ivan / Charles, Julie / Kaatz, Martin / Sznol, Mario / Weber, Jeffrey S / Shoushtari, Alexander N / Ruisi, Mary / Jiang, Joel / Wolchok, Jedd D. ·Sandra P. D'Angelo, Alexander N. Shoushtari, and Jedd D. Wolchok, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY · James Larkin, Royal Marsden Hospital, London · Paul Lorigan, University of Manchester, Manchester, United Kingdom · Jeffrey A. Sosman, Vanderbilt University Medical Center, Nashville, TN · Celeste Lebbé, Saint-Louis Hospital, Institut National de la Santé et de la Recherche Médicale U976, Université Paris Diderot, Paris · Julie Charles, Grenoble University Hospital, Grenoble Alps University, Grenoble, France · Benjamin Brady, Cabrini Health, Melbourne, Australia · Bart Neyns, Universitair Ziekenhuis Brussel, Brussels, Belgium · Henrik Schmidt, Århus University, Åarhus, Denmark · Jessica C. Hassel, University Hospital Heidelberg, Heidelberg · Peter Mohr, Elbe Kliniken Buxtehude, Buxtehude · Martin Kaatz, SRH Waldklinikum Gera, University Hospital Jena, Jena, Germany · F. Stephen Hodi, Dana-Farber Cancer Institute, Boston, MA · Kerry J. Savage, BC Cancer Agency, University of British Columbia, Vancouver · Wilson H. Miller Jr, Lady Davis Institute and Jewish General Hospital, McGill University, Montreal, Canada · Ivan Marquez-Rodas, Hospital General Universitario Gregorio Marañón, Madrid, Spain · Mario Sznol, Yale University School of Medicine and Smilow Cancer Center, Yale-New Haven Hospital, New Haven, CT · Jeffrey S. Weber, Moffitt Cancer Center, Tampa, FL · and Mary Ruisi and Joel Jiang, Bristol-Myers Squibb, Princeton, NJ. ·J Clin Oncol · Pubmed #28056206.

ABSTRACT: Purpose Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy and safety of nivolumab (a programmed death-1 checkpoint inhibitor), alone or combined with ipilimumab (a cytotoxic T-lymphocyte antigen-4 checkpoint inhibitor), have not been reported in this rare melanoma subtype. Patients and Methods Data were pooled from 889 patients who received nivolumab monotherapy in clinical studies, including phase III trials; 86 (10%) had mucosal melanoma and 665 (75%) had cutaneous melanoma. Data were also pooled for patients who received nivolumab combined with ipilimumab (n = 35, mucosal melanoma; n = 326, cutaneous melanoma). Results Among patients who received nivolumab monotherapy, median progression-free survival was 3.0 months (95% CI, 2.2 to 5.4 months) and 6.2 months (95% CI, 5.1 to 7.5 months) for mucosal and cutaneous melanoma, with objective response rates of 23.3% (95% CI, 14.8% to 33.6%) and 40.9% (95% CI, 37.1% to 44.7%), respectively. Median progression-free survival in patients treated with nivolumab combined with ipilimumab was 5.9 months (95% CI, 2.8 months to not reached) and 11.7 months (95% CI, 8.9 to 16.7 months) for mucosal and cutaneous melanoma, with objective response rates of 37.1% (95% CI, 21.5% to 55.1%) and 60.4% (95% CI, 54.9% to 65.8%), respectively. For mucosal and cutaneous melanoma, respectively, the incidence of grade 3 or 4 treatment-related adverse events was 8.1% and 12.5% for nivolumab monotherapy and 40.0% and 54.9% for combination therapy. Conclusion To our knowledge, this is the largest analysis of data for anti-programmed death-1 therapy in mucosal melanoma to date. Nivolumab combined with ipilimumab seemed to have greater efficacy than either agent alone, and although the activity was lower in mucosal melanoma, the safety profile was similar between subtypes.

7 Article [Acantholytic dermatosis in patients treated by vemurafenib: 2 cases]. 2014

Sabatier-Vincent, M / Charles, J / Pinel, N / Challende, I / Claeys, A / Leccia, M-T. ·Clinique de dermatologie et photobiologie, hôpital Nord, CHU de Grenoble, Cs 10217, boulevard de la-Chantourne-La-Tronche, 38043 Grenoble cedex 9, France. Electronic address: msabatiervincent@chu-grenoble.fr. · Clinique de dermatologie et photobiologie, hôpital Nord, CHU de Grenoble, Cs 10217, boulevard de la-Chantourne-La-Tronche, 38043 Grenoble cedex 9, France. · Département d'anatomie pathologique, CHU de Grenoble, Cs 10217, 38043 Grenoble cedex 9, France. ·Ann Dermatol Venereol · Pubmed #25442474.

ABSTRACT: BACKGROUND: Acantholytic dyskeratosis under BRAF inhibitors are dermatological diseases rarely reported to date. PATIENTS AND METHODS: We report 2 cases of acantholytic dyskeratosis, reaching the trunk and the seborrheic zones, not itchy, appeared one month after the introduction of vemurafenib. The histological analysis was typical of a "Grover-like rash" for the 2 patients. DISCUSSION: The appearance of acantholytic dyskeratosis under vemurafenib, a BRAF inhibitor, seems related with a paradoxical activation of the MAP-kinases pathway and with a growth acceleration of lesions in which RAS mutations of keratinocytes. Theses dermatoses seem also to occur with dabrafenib. CONCLUSION: The patients treated by BRAF inhibitors (vemurafenib and dabrafenib) can present acantholytic dyskeratosis. The arisen of this mild dermatosis does not question, of course, the continuation of the treatment. These cutaneous manifestations can be managed with emollients.

8 Article Imiquimod inhibits melanoma development by promoting pDC cytotoxic functions and impeding tumor vascularization. 2014

Aspord, Caroline / Tramcourt, Laetitia / Leloup, Claire / Molens, Jean-Paul / Leccia, Marie-Therese / Charles, Julie / Plumas, Joel. ·R&D Laboratory, Etablissement Français du Sang Rhône-Alpes, La Tronche, France; University Joseph Fourier, Grenoble, France; Immunobiology & Immunotherapy of Cancers, U823, INSERM, La Tronche, France. Electronic address: carolineaspord@yahoo.com. · R&D Laboratory, Etablissement Français du Sang Rhône-Alpes, La Tronche, France; University Joseph Fourier, Grenoble, France; Immunobiology & Immunotherapy of Cancers, U823, INSERM, La Tronche, France. · University Joseph Fourier, Grenoble, France; Immunobiology & Immunotherapy of Cancers, U823, INSERM, La Tronche, France; Department of Dermatology, Grenoble University Hospital, Grenoble, France. ·J Invest Dermatol · Pubmed #24751730.

ABSTRACT: Imiquimod (IMQ) is a synthetic Toll-like receptor (TLR7/8) ligand that can trigger antiviral and antitumor activities. Despite evidence of potent therapeutic effects, the clinical use of IMQ in melanoma is impeded by incomplete understanding of its mechanisms of action. Mice and humans differ in many aspects of immunity, including TLR7 expression patterns, thus impeding the use of mouse models in translating discoveries into clinical applications. In this article, we investigated the mechanisms behind IMQ effects in vivo in a human context of melanoma and immunity using an innovative melanoma-bearing humanized mouse model. In this model, IMQ strongly inhibited melanoma tumor development through prompt mobilization of plasmacytoid dendritic cells and by triggering their cytotoxic functions, and through upregulation of expression of type 1 IFN response genes. IMQ also drastically impeded tumor vascularization by inducing the downregulation of angiogenic factors vascular endothelial growth factor, angiogenin, IL-8, and fibroblast growth factor. Our results revealed the short- and long-term multifactorial effects of IMQ converging toward inhibition of melanoma development. By providing a better understanding of the mechanisms of action of IMQ in melanoma, our study opens the way for its further clinical use in the treatment of metastatic melanoma.

9 Article Plasmacytoid dendritic cells support melanoma progression by promoting Th2 and regulatory immunity through OX40L and ICOSL. 2013

Aspord, Caroline / Leccia, Marie-Therese / Charles, Julie / Plumas, Joel. ·Authors' Affiliations: Department of Dermatology, Grenoble University Hospital, Grenoble, France. ·Cancer Immunol Res · Pubmed #24778133.

ABSTRACT: Even though melanoma is considered to be one of the most immunogenic solid tumors, handling its development remains a challenge. The basis for such escape from antitumor immune control has not yet been documented. Plasmacytoid dendritic cells (pDC) are emerging as crucial but still enigmatic cells in cancer. In melanoma, the function of tumor-infiltrating pDCs remains poorly explored. We investigated the pathophysiologic role of pDCs in melanoma, both ex vivo from a large cohort of melanoma patients and in vivo in melanoma-bearing humanized mice. pDCs were found in high proportions in cutaneous melanoma and tumor-draining lymph nodes, yet associated with poor clinical outcome. We showed that pDCs migrating to the tumor microenvironment displayed particular features, subsequently promoting proinflammatory Th2 and regulatory immune profiles through OX40L and ICOSL expression. Elevated frequencies of interleukin (IL)-5-, IL-13- and IL-10-producing T cells in patients with melanoma correlated with high proportions of OX40L- and ICOSL-expressing pDCs. Strikingly TARC/CCL17, MDC/CCL22, and MMP-2 found in the melanoma microenvironment were associated with pDC accumulation, OX40L and ICOSL modulation, and/or early relapse. Thus, melanoma actively exploits pDC plasticity to promote its progression. By identifying novel insights into the mechanism of hijacking of immunity by melanoma, our study exposes potential for new therapeutic opportunities.

10 Article Identification of a novel complex BRAF mutation associated with major clinical response to vemurafenib in a patient with metastatic melanoma. 2013

Busser, Benoit / Leccia, Marie Therese / Gras-Combe, Guillaume / Bricault, Ivan / Templier, Isabelle / Claeys, Antoine / Richard, Marie Jeanne / de Fraipont, Florence / Charles, Julie. ·Institut Albert Bonniot INSERM/UJF U823, Grenoble, France. · Department of Neurosurgery, CHRU Grenoble University Hospital, Grenoble, France. · Department of Medical Imaging, CHRU Grenoble University Hospital, Grenoble, France. · Department of Dermatology, CHRU Grenoble University Hospital, Grenoble, France. · Department of Cancer Clinical Chemistry, CHRU Grenoble University Hospital, Grenoble, France. ·JAMA Dermatol · Pubmed #24108467.

ABSTRACT: IMPORTANCE: There is an increasing interest in BRAF V600 mutations in melanomas and their associated sensitivity to vemurafenib, a BRAF inhibitor. However, physicians cannot find information in the literature about vemurafenib response for rare and/or atypical BRAF mutations. OBSERVATIONS: We describe the identification of a novel complex BRAF mutation associated with major clinical response to vemurafenib in a patient with metastatic melanoma. Using a pyrosequencing method, we determined that the tumor positive for mutated BRAF, uncovering a novel c.1799_1803delinsAT; p.V600-K601>D variant. We uncovered this atypical BRAF mutation with 2 different sequencing methods, both in the primary lesion and in 1 metastasis. The patient was immediately treated with vemurafenib as monotherapy and achieved a prolonged (5.5-month) positive response. CONCLUSIONS AND RELEVANCE: We analyzed the consequences of the BRAF V600-K601>D mutation in terms of amino acids. We referred to the published data and databases to screen chemical properties of well-known BRAF V600 mutations and other complex BRAF mutations to find common features of activated BRAF mutations. Importantly, we highlighted that both the site of the mutation and the involved amino acids are important to predict vemurafenib response. Our conclusion is that complex BRAF mutation surrounding codon 600 could also be sensitive to BRAF inhibitors.

11 Article HLA-A(*)0201(+) plasmacytoid dendritic cells provide a cell-based immunotherapy for melanoma patients. 2012

Aspord, Caroline / Leccia, Marie-Therese / Salameire, Dimitri / Laurin, David / Chaperot, Laurence / Charles, Julie / Plumas, Joel. ·Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France. Electronic address: carolineaspord@yahoo.com. · University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; Department of Dermatology, Michallon Hospital, Pôle Pluridisciplinaire de Médecine, Grenoble, France. · University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; Anatomo-cytopathology, Michallon Hospital, Grenoble, France. · Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France. · Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France; University Joseph Fourier, Grenoble, France; INSERM U823, Immunobiology & Immunotherapy of Cancers, La Tronche, France; University College London, Cancer Institute, London, UK. ·J Invest Dermatol · Pubmed #22696054.

ABSTRACT: Several sources of evidence suggest that tumor-specific T cells have the potential to control melanoma tumors. Current active and adoptive therapeutic approaches to elicit such T cells are either not sufficiently clinically efficient or require fastidious processes that impede their extensive clinical use. As plasmacytoid dendritic cells (pDCs) have a crucial role in triggering antitumor immunity especially in melanoma, we explored their potential as a cell-based approach for melanoma immunotherapy. An irradiated human HLA-A(*)0201(+) pDC line loaded with peptides derived from the major melanoma tumor antigens, MelA/MART-1, gp100/pmel17, tyrosinase, and MAGE-A3, was used to trigger functional multi-specific T cells ex vivo from peripheral blood mononuclear cells and tumor-infiltrating lymphocytes from stage I-IV HLA-A(*)0201(+) melanoma patients. pDCs loaded with melanoma-derived peptides promptly induced high levels of melanoma tumor-specific T cells from both sources. pDC-primed central/effector memory antitumor T cells were highly functional as indicated by the specific IFNγ secretion and membrane CD107 expression upon stimulation. Cells also exhibited strong cytotoxicity toward semi-allogeneic melanoma cells and patient-derived tumor cells. The simple design and potent efficacy of this promising approach provides a preclinical basis for the development of a pDC-based vaccine and an alternative means to produce tumor-specific T cells for adoptive cellular immunotherapy in melanoma patients.

12 Article [GENiusVac, a novel antitumor vaccine strategy based on allogeneic plasmacytoid dendritic cells]. 2011

Aspord, C / Charles, J / Leccia, M-T / Laurin, D / Richard, M-J / Chaperot, L / Plumas, J. ·Inserm U823, Établissement français du sang (EFS) Rhone-Alpes, R&D Laboratory, 38701 La Tronche, France. carolineaspord@yahoo.com ·Rev Med Interne · Pubmed #21429635.

ABSTRACT: The development of effective vaccines against cancer and viruses still remains a challenge. Many immunotherapeutic strategies have been developed but without sufficient therapeutic success. Plasmacytoid dendritic cells (pDC) play a crucial role in antitumor and antiviral responses. Despite their outstanding functional properties, their therapeutic potential has not yet been worked out. We propose a new immunotherapeutic strategy based on a pDC cell line irradiated and pulsed with tumor or viral antigens. GENiusVac allows the induction of multispecific and highly functional cytotoxic cell responses directed against viral or tumor targets. We demonstrated the potential of this strategy in vitro, its therapeutic efficacy in vivo in a humanized mouse model, and its clinical relevance ex vivo from melanoma patients' cells. GENiusVac highlights pDCs as potent vector of immunotherapy and provide a way to exploit them in cell therapy to fight cancer or chronic viral infections.

13 Article A novel cancer vaccine strategy based on HLA-A*0201 matched allogeneic plasmacytoid dendritic cells. 2010

Aspord, Caroline / Charles, Julie / Leccia, Marie-Therese / Laurin, David / Richard, Marie-Jeanne / Chaperot, Laurence / Plumas, Joel. ·Etablissement Français du Sang Rhone-Alpes, R&D Laboratory, La Tronche, France. carolineaspord@yahoo.com ·PLoS One · Pubmed #20454561.

ABSTRACT: BACKGROUND: The development of effective cancer vaccines still remains a challenge. Despite the crucial role of plasmacytoid dendritic cells (pDCs) in anti-tumor responses, their therapeutic potential has not yet been worked out. We explored the relevance of HLA-A*0201 matched allogeneic pDCs as vectors for immunotherapy. METHODS AND FINDINGS: Stimulation of PBMC from HLA-A*0201(+) donors by HLA-A*0201 matched allogeneic pDCs pulsed with tumor-derived peptides triggered high levels of antigen-specific and functional cytotoxic T cell responses (up to 98% tetramer(+) CD8 T cells). The pDC vaccine demonstrated strong anti-tumor therapeutic in vivo efficacy as shown by the inhibition of tumor growth in a humanized mouse model. It also elicited highly functional tumor-specific T cells ex-vivo from PBMC and TIL of stage I-IV melanoma patients. Responses against MelA, GP100, tyrosinase and MAGE-3 antigens reached tetramer levels up to 62%, 24%, 85% and 4.3% respectively. pDC vaccine-primed T cells specifically killed patients' own autologous melanoma tumor cells. This semi-allogeneic pDC vaccine was more effective than conventional myeloid DC-based vaccines. Furthermore, the pDC vaccine design endows it with a strong potential for clinical application in cancer treatment. CONCLUSIONS: These findings highlight HLA-A*0201 matched allogeneic pDCs as potent inducers of tumor immunity and provide a promising immunotherapeutic strategy to fight cancer.

14 Article Characterization of circulating dendritic cells in melanoma: role of CCR6 in plasmacytoid dendritic cell recruitment to the tumor. 2010

Charles, Julie / Di Domizio, Jérémy / Salameire, Dimitri / Bendriss-Vermare, Nathalie / Aspord, Caroline / Muhammad, Ramzan / Lefebvre, Christine / Plumas, Joël / Leccia, Marie-Thérèse / Chaperot, Laurence. ·INSERM U823, Centre de Recherche Albert Bonniot, Immunobiologie et Immunothérapie des Cancers, Université Joseph Fourier, R&D Laboratory, EFS Rhônes-Alpes, 29 Avenue Maquis du Gresivaudan, La Tronche, France. ·J Invest Dermatol · Pubmed #20220766.

ABSTRACT: Dendritic cells (DCs) are central cells in the development of antitumor immune responses, but the number and function of these cells can be altered in various cancers. Whether these cells are affected during the development of melanoma is not known. We investigated the presence, phenotype, and functionality of circulating myeloid DCs (MDCs) and plasmacytoid DCs (PDCs) in newly diagnosed melanoma patients, compared to controls. The frequencies of PDCs and MDCs were equivalent in melanoma patients as compared with normal subjects. Both circulating DC subsets were immature, but on ex vivo stimulation with R848 they efficiently upregulated their expression of costimulatory molecules. We found that circulating DCs from melanoma patients and controls displayed similar pattern of expression of the chemokine receptors CXCR3, CXCR4, CCR7, and CCR10. Strikingly, PDCs from melanoma patients expressed higher levels of CCR6 than control PDCs, and were able to migrate toward CCL20. Further data showed that CCR6-expressing PDCs were present in melanoma primary lesions, and that CCL20 was produced in melanoma tumors. These results suggest that PDCs and MDCs are functional in melanoma patients at the time of diagnosis, and that CCL20 may participate to their recruitment from the blood to the tumor.

15 Minor Twenty-two cutaneous primary melanomas in a patient with high genetic predisposition to melanoma receiving levodopa therapy for Parkinson's disease. 2009

Charles, Julie / Templier, Isabelle / Leroux, Dominique / Salameire, Dimitri / Robert, Caroline / Lantuejoul, Sylvie / Leccia, Marie-Therese. · ·Pigment Cell Melanoma Res · Pubmed #19708914.

ABSTRACT: -- No abstract --