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DOI: 10.1055/s-0038-1645020
Adoptive Cellular Immunotherapy using CD1a CART-cells for Treatment of Cortical Pediatric T-Cell Acute Lymphoblastic Leukemia
Publikationsverlauf
Publikationsdatum:
08. Mai 2018 (online)
(Pre)-clinical reports have demonstrated that chimeric antigen receptors efficiently redirect T cells (CARTs) against a variety of malignancies, including CD19+ B-cell acute lymphoblastic leukemia (B-ALL). However, CAR T cell-based immunotherapy for other pediatric malignancies remains more challenging. Pediatric T-cell ALL (T-ALL) is a heterogeneous clonal disease arising early during T-cell development. CD1a is a cortical T-cell antigen always present in cortical T-ALL but absent in normal circulating T-cells. The choice of the antigen to be targeted is instrumental for the effective and safe development of adoptive immunotherapies.
CARCD1a is stably expressed in primary T-cells and it has been tested in a battery of in vitro assays. PB-MNCs were activated and infected and later CAR transduction was successfully detected by GFP and anti-scFv in activated CD4+ and CD8+ T-cells. CARCD1a-expressing activated T-cells were expanded extensively in vitro, and they exerted robust and specific in vitro cytotoxicity against CD1a positive T-ALL cell lines associated to a massive release of pro-inflammatory cytokines. CAR T-based cell immunotherapy for refractory/relapsed T-ALL will be a treatment breakthrough because there are no current alternative treatments.