{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T13:44:13Z","timestamp":1778852653859,"version":"3.51.4"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"9","license":[{"start":{"date-parts":[[2014,11,1]],"date-time":"2014-11-01T00:00:00Z","timestamp":1414800000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Current treatment of chronic lymphocytic leukemia (CLL) patients often results in life-threatening immunosuppression. Furthermore, CLL is still an incurable disease due to the persistence of residual leukemic cells. These patients may therefore benefit from immunotherapy approaches aimed at immunoreconstitution and\/or the elimination of residual disease following chemotherapy. For these purposes, we designed a simple GMP-compliant protocol for ex vivo expansion of normal T cells from CLL patients\u2019 peripheral blood for adoptive therapy, using bispecific Ab blinatumomab (CD3 \u00d7 CD19), acting both as T cell stimulator and CLL depletion agent, and human rIL-2. Starting from only 10 ml CLL peripheral blood, a mean 515 \u00d7 106 CD3+ T cells were expanded in 3 wk. The resulting blinatumomab-expanded T cells (BET) were polyclonal CD4+ and CD8+ and mostly effector and central memory cells. The Th1 subset was slightly prevalent over Th2, whereas Th17 and T regulatory cells were &amp;lt;1%. CMV-specific clones were detected in equivalent proportion before and after expansion. Interestingly, BET cells had normalized expression of the synapse inhibitors CD272 and CD279 compared with starting T cells and were cytotoxic against CD19+ targets in presence of blinatumomab in vitro. In support of their functional capacity, we observed that BET, in combination with blinatumomab, had significant therapeutic activity in a systemic human diffuse large B lymphoma model in NOD-SCID mice. We propose BET as a therapeutic tool for immunoreconstitution of heavily immunosuppressed CLL patients and, in combination with bispecific Ab, as antitumor immunotherapy.<\/jats:p>","DOI":"10.4049\/jimmunol.1401550","type":"journal-article","created":{"date-parts":[[2014,9,30]],"date-time":"2014-09-30T05:51:49Z","timestamp":1412056309000},"page":"4739-4747","source":"Crossref","is-referenced-by-count":25,"title":["A Novel Method Using Blinatumomab for Efficient, Clinical-Grade Expansion of Polyclonal T Cells for Adoptive Immunotherapy"],"prefix":"10.1093","volume":"193","author":[{"given":"Jos\u00e9e","family":"Golay","sequence":"first","affiliation":[{"name":"Centro di Terapia Cellulare, \u201cG. Lanzani,\u201d USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII , 24127 Bergamo ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Centro di Terapia Cellulare, \u201cG. Lanzani,\u201d USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII , 24127 Bergamo ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianmaria","family":"Borleri","sequence":"additional","affiliation":[{"name":"Centro Trapianto Midollo Osseo, USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII , 24127 Bergamo ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michela","family":"Bonzi","sequence":"additional","affiliation":[{"name":"Centro di Terapia Cellulare, \u201cG. Lanzani,\u201d USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII , 24127 Bergamo ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rut","family":"Valgardsdottir","sequence":"additional","affiliation":[{"name":"Centro di Terapia Cellulare, \u201cG. Lanzani,\u201d USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII , 24127 Bergamo ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachele","family":"Alzani","sequence":"additional","affiliation":[{"name":"Nerviano Medical Sciences , 20014 Nerviano ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Cribioli","sequence":"additional","affiliation":[{"name":"Nerviano Medical Sciences , 20014 Nerviano ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Albanese","sequence":"additional","affiliation":[{"name":"Nerviano Medical Sciences , 20014 Nerviano ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Pesenti","sequence":"additional","affiliation":[{"name":"Nerviano Medical Sciences , 20014 Nerviano ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Chiara","family":"Finazzi","sequence":"additional","affiliation":[{"name":"Centro Trapianto Midollo Osseo, USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII , 24127 Bergamo ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Quaresmini","sequence":"additional","affiliation":[{"name":"Centro Trapianto Midollo Osseo, USC Ematologia, Azienda Ospedaliera Papa Giovanni XXIII , 24127 Bergamo ,","place":["Italy"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk","family":"Nagorsen","sequence":"additional","affiliation":[{"name":"Global Clinical Development, Amgen , Thousand Oaks, CA 91320"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martino","family":"Introna","sequence":"additional","affiliation":[{"name":"Centro di Terapia Cellulare, \u201cG. 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