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Morgan, Richard A; Chinnasamy, Nachimuthu; Abate-Daga, Daniel; Gros, Alena; Robbins, Paul F; Zheng, Zhili; Dudley, Mark E; Feldman, Steven A; Yang, James C; Sherry, Richard M; Phan, Giao Q; Hughes, Marybeth S; Kammula, Udai S; Miller, Akemi D; Hessman, Crystal J; Stewart, Ashley A; Restifo, Nicholas P; Quezado, Martha M; Alimchandani, Meghna; Rosenberg, Avi Z; Nath, Avindra; Wang, Tongguang; Bielekova, Bibiana; Wuest, Simone C; Akula, Nirmala; McMahon, Francis J; Wilde, Susanne; Mosetter, Barbara; Schendel, Dolores J; Laurencot, Carolyn M; Rosenberg, Steven A
Journal of immunotherapy, 02/2013, Letnik: 36, Številka: 2Journal Article
Nine cancer patients were treated with adoptive cell therapy using autologous anti-MAGE-A3 T-cell receptors (TCR)-engineered T cells. Five patients experienced clinical regression of their cancers including 2 on-going responders. Beginning 1-2 days postinfusion, 3 patients (#'s 5, 7, and 8) experienced mental status changes, and 2 patients (5 and 8) lapsed into comas and subsequently died. Magnetic resonance imagining analysis of patients 5 and 8 demonstrated periventricular leukomalacia, and examination of their brains at autopsy revealed necrotizing leukoencephalopathy with extensive white matter defects associated with infiltration of CD3(+)/CD8(+) T cells. Patient 7, developed Parkinson-like symptoms, which resolved over 4 weeks and fully recovered. Immunohistochemical staining of patient and normal brain samples demonstrated rare positively staining neurons with an antibody that recognizes multiple MAGE-A family members. The TCR used in this study recognized epitopes in MAGE-A3/A9/A12. Molecular assays of human brain samples using real-time quantitative-polymerase chain reaction, Nanostring quantitation, and deep-sequencing indicated that MAGE-A12 was expressed in human brain (and possibly MAGE-A1, MAGE-A8, and MAGE-A9). This previously unrecognized expression of MAGE-A12 in human brain was possibly the initiating event of a TCR-mediated inflammatory response that resulted in neuronal cell destruction and raises caution for clinical applications targeting MAGE-A family members with highly active immunotherapies.
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Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Vir: Osebne bibliografije
in: SICRIS
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