{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T22:39:50Z","timestamp":1790375990781,"version":"4.1.0"},"reference-count":46,"publisher":"American Society of Hematology","issue":"20","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,10,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The treatment of advanced-stage cutaneous T-cell lymphoma (CTCL) remains an unmet medical need. Mogamulizumab, anti-KIR3DL2, and brentuximab vedotin (BV), an anti-CD30 antibody\u2013drug conjugate (ADC) coupled with monomethyl-auristatin-E (MMAE), provided encouraging results, but new targeted therapies are needed. Inducible T-cell costimulator (ICOS), a T-cell costimulatory receptor, is a promising therapeutic target, not only because it is expressed by malignant T cells in CTCL but also because of its connection with the suppressive activity of regulatory T (Treg) cells. Immunohistochemical analysis revealed that ICOS was widely expressed by malignant cells in skin biopsy specimens from 52 patients with mycosis fungoides and S\u00e9zary syndrome (SS), as well as in involved node biopsy specimens from patients with SS. Furthermore, flow cytometry demonstrated its strong expression by circulating tumor cells in all our patients with SS. Percentages of ICOS+ Treg cells were significantly higher in patients with SS than in healthy donors. We then investigated the preclinical efficacy of anti-ICOS ADCs generated by coupling murine anti-ICOS monoclonal antibodies with MMAE and pyrrolobenzodiazepine. In 3 CTCL cell lines (Myla, MJ, and HUT78), we observed a significant dose-dependent decrease in cell viability in the presence of anti-ICOS ADCs. In addition, anti-ICOS-MMAE ADCs had an in vitro and in vivo efficacy superior to BV in a mouse xenograft model (MyLa). Finally, we assessed the efficacy of anti-ICOS ADCs in ICOS+ patient-derived xenografts from patients with SS and angioimmunoblastic T-cell lymphoma. Collectively, our findings provide the preliminary basis for a therapeutic trial.<\/jats:p>","DOI":"10.1182\/bloodadvances.2020002395","type":"journal-article","created":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T15:37:35Z","timestamp":1603467455000},"page":"5203-5214","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":38,"title":["ICOS is widely expressed in cutaneous T-cell lymphoma, and its targeting promotes potent killing of malignant cells"],"prefix":"10.1182","volume":"4","author":[{"given":"Florent","family":"Amatore","sequence":"first","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille, INSERM U1068, Centre National de la Recherche Scientifique U7258, Aix Marseille Universit\u00e9, Institut Paoli-Calmettes, Marseille, France;"},{"name":"Department of Dermatology and Skin Cancers, H\u00f4pital de la Timone, Aix Marseille Universit\u00e9, Marseille, France;"},{"name":"Department of Dermatology, Aix Marseille University, Assistance Publique\u2013H\u00f4pitaux de Marseille, H\u00f4pital Nord, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0111-7422","authenticated-orcid":false,"given":"Nicolas","family":"Ortonne","sequence":"additional","affiliation":[{"name":"Department of Pathology and INSERM U955 Team 9 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6573-633X","authenticated-orcid":false,"given":"Marc","family":"Lopez","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille, INSERM U1068, Centre National de la Recherche Scientifique U7258, Aix Marseille Universit\u00e9, Institut Paoli-Calmettes, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florence","family":"Orlanducci","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille, INSERM U1068, Centre National de la Recherche Scientifique U7258, Aix Marseille Universit\u00e9, Institut Paoli-Calmettes, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9my","family":"Castellano","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille, INSERM U1068, Centre National de la Recherche Scientifique U7258, Aix Marseille Universit\u00e9, Institut Paoli-Calmettes, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia","family":"Ingen-Housz-Oro","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Henri-Mondor, Cr\u00e9teil, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6902-9288","authenticated-orcid":false,"given":"Amandine","family":"De 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Universit\u00e9, Institut Paoli-Calmettes, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5359-7099","authenticated-orcid":false,"given":"Yves","family":"Collette","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Canc\u00e9rologie de Marseille, INSERM U1068, Centre National de la Recherche Scientifique U7258, Aix Marseille Universit\u00e9, Institut Paoli-Calmettes, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00e9da","family":"Bouabdallah","sequence":"additional","affiliation":[{"name":"Department of Hematology, Institut Paoli-Calmettes, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9923-4808","authenticated-orcid":false,"given":"Jean-Marc","family":"Schiano","sequence":"additional","affiliation":[{"name":"Department of Hematology, Institut Paoli-Calmettes, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Aix Marseille University, Assistance Publique\u2013H\u00f4pitaux de Marseille, H\u00f4pital Nord, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Jacques","family":"Grob","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Skin Cancers, H\u00f4pital de la Timone, Aix Marseille Universit\u00e9, Marseille, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Gaulard","sequence":"additional","affiliation":[{"name":"Department of Pathology and INSERM U955 Team 9 and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Bagot","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Saint-Louis Hospital, AP-HP, Paris University, INSERM U976, Paris, France; 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