IRIS – Institutional Research Information System
IRIS è il sistema di gestione della ricerca dell’Università degli Studi di Milano-Bicocca.Il repository BOA è il modulo del sistema dedicato alla raccolta e alla disseminazione della produzione scientifica di Ateneo. Le pubblicazioni sono ricercabili per parola chiave attraverso il box nella barra orizzontale in alto oppure, mediante il pulsante Sfoglia, per "Afferenza", "Autore", "Titolo", "Tipologia" o "Settore scientifico-disciplinare".
IRIS contiene inoltre alcuni moduli dedicati alla registrazione dei progetti e dei contratti, e alla reportistica avanzata per le attività di valutazione della ricerca
EnglishChimeric antigen receptor (CAR)-redirected T lymphocytes are a promising immunotherapeutic approach and object of pre-clinical evaluation for the treatment of acute myeloid leukemia (AML). We developed a CAR against CD123, overexpressed on AML blasts and leukemic stem cells. However, potential recognition of low CD123-positive healthy tissues, through the on-target, off-tumor effect, limits safe clinical employment of CAR-redirected T cells. Therefore, we evaluated the effect of context-dependent variables capable of modulating CAR T cell functional profiles, such as CAR binding affinity, CAR expression, and target antigen density. Computational structural biology tools allowed for the design of rational mutations in the anti-CD123 CAR antigen binding domain that altered CAR expression and CAR binding affinity without affecting the overall CAR design. We defined both lytic and activation antigen thresholds, with early cytotoxic activity unaffected by either CAR expression or CAR affinity tuning but later effector functions impaired by low CAR expression. Moreover, the anti-CD123 CAR safety profile was confirmed by lowering CAR binding affinity, corroborating CD123 is a good therapeutic target antigen. Overall, full dissection of these variables offers suitable anti-CD123 CAR design optimization for the treatment of AML.
Arcangeli, S., Rotiroti, M., Bardelli, M., Simonelli, L., Magnani, C., Biondi, A., et al. (2017). Balance of Anti-CD123 Chimeric Antigen Receptor Binding Affinity and Density for the Targeting of Acute Myeloid Leukemia. MOLECULAR THERAPY, 25(8), 1933-1945.
| Citazione: | Arcangeli, S., Rotiroti, M., Bardelli, M., Simonelli, L., Magnani, C., Biondi, A., et al. (2017). Balance of Anti-CD123 Chimeric Antigen Receptor Binding Affinity and Density for the Targeting of Acute Myeloid Leukemia. MOLECULAR THERAPY, 25(8), 1933-1945. |
| Tipo: | Articolo in rivista - Articolo scientifico |
| Carattere della pubblicazione: | Scientifica |
| Presenza di un coautore afferente ad Istituzioni straniere: | Si |
| Titolo: | Balance of Anti-CD123 Chimeric Antigen Receptor Binding Affinity and Density for the Targeting of Acute Myeloid Leukemia |
| Autori: | Arcangeli, S; Rotiroti, M; Bardelli, M; Simonelli, L; Magnani, C; Biondi, A; Biagi, E; Tettamanti, S; Varani, L |
| Autori: | |
| Data di pubblicazione: | 2017 |
| Lingua: | English |
| Rivista: | MOLECULAR THERAPY |
| Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.ymthe.2017.04.017 |
| Appare nelle tipologie: | 01 - Articolo su rivista |
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|---|---|---|---|---|
| 10281-152515.pdf | Publisher's version | Open Access Visualizza/Apri |
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