{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T21:04:28Z","timestamp":1765487068926,"version":"build-2065373602"},"reference-count":53,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["21648","ROL 32567","Ricerca Corrente 2022\u20132024"],"award-info":[{"award-number":["21648","ROL 32567","Ricerca Corrente 2022\u20132024"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007388","name":"Compagnia di San Paolo","doi-asserted-by":"publisher","award":["21648","ROL 32567","Ricerca Corrente 2022\u20132024"],"award-info":[{"award-number":["21648","ROL 32567","Ricerca Corrente 2022\u20132024"]}],"id":[{"id":"10.13039\/100007388","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Italian Ministry of Health","award":["21648","ROL 32567","Ricerca Corrente 2022\u20132024"],"award-info":[{"award-number":["21648","ROL 32567","Ricerca Corrente 2022\u20132024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Relevant advances have been made in the management of relapsed\/refractory (r\/r) Hodgkin Lymphomas (HL) with the use of the anti-CD30 antibody\u2013drug conjugate (ADC) brentuximab\u2013vedotin (Bre\u2013Ved). Unfortunately, most patients eventually progress despite the excellent response rates and tolerability. In this report, we describe an ADC composed of the aminobisphosphonate zoledronic acid (ZA) conjugated to Bre\u2013Ved by binding the free amino groups of this antibody with the phosphoric group of ZA. Liquid chromatography\u2013mass spectrometry, inductively coupled plasma\u2013mass spectrometry, and matrix-assisted laser desorption ionization\u2013mass spectrometry analyses confirmed the covalent linkage between the antibody and ZA. The novel ADC has been tested for its reactivity with the HL\/CD30+ lymphoblastoid cell lines (KMH2, L428, L540, HS445, and RPMI6666), showing a better titration than native Bre\u2013Ved. Once the HL-cells are entered, the ADC co-localizes with the lysosomal LAMP1 in the intracellular vesicles. Also, this ADC exerted a stronger anti-proliferative and pro-apoptotic (about one log fold) effect on HL-cell proliferation compared to the native antibody Bre\u2013Ved. Eventually, Bre\u2013Ved\u2013ZA ADC, in contrast with the native antibody, can trigger the proliferation and activation of cytolytic activity of effector-memory V\u03b42 T-lymphocytes against HL-cell lines. These findings may support the potential use of this ADC in the management of r\/r HL.<\/jats:p>","DOI":"10.3390\/cells13100862","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T06:53:49Z","timestamp":1715928829000},"page":"862","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Antibody\u2013Drug Conjugate Made of Zoledronic Acid and the Anti-CD30 Brentuximab\u2013Vedotin Exert Anti-Lymphoma and Immunostimulating Effects"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-4503-3610","authenticated-orcid":false,"given":"Feliciana","family":"Morelli","sequence":"first","affiliation":[{"name":"Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3023-0213","authenticated-orcid":false,"given":"Serena","family":"Matis","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9769-0954","authenticated-orcid":false,"given":"Roberto","family":"Benelli","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Salvini","sequence":"additional","affiliation":[{"name":"Fondazione Toscana Life Sciences, Technology Facilities and Mass Spectrometry Unit, 53100 Siena, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Raffaella","family":"Zocchi","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplants and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1860-430X","authenticated-orcid":false,"given":"Alessandro","family":"Poggi","sequence":"additional","affiliation":[{"name":"Molecular Oncology and Angiogenesis Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nrc3245","article-title":"The immune contexture in human tumours: Impact on clinical outcome","volume":"12","author":"Fridman","year":"2012","journal-title":"Nat. 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