Maciocia, Paul Michael;
Wawrzyniecka, Patrycja A;
Maciocia, Nicola C;
Burley, Amy;
Karpanasamy, Thaneswari;
Devereaux, Sam;
Hoekx, Malika;
... Mansour, Marc R; + view all
(2022)
Anti-CCR9 chimeric antigen receptor T cells for T-cell acute lymphoblastic leukemia.
Blood
, 140
(1)
pp. 25-37.
10.1182/blood.2021013648.
Preview |
Text
blood.2021013648.pdf - Accepted Version Download (1MB) | Preview |
Abstract
T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of immature T lymphocytes, associated with higher rates of induction failure in comparison to B-ALL. The potent immunotherapeutic approaches applied in B-ALL, which have revolutionized the treatment paradigm, have proven more challenging in T-ALL, largely due to a lack of target antigens expressed on malignant but not healthy T cells. Unlike B cell depletion, T cell aplasia is highly toxic. Here, we demonstrate that the chemokine receptor CCR9 is expressed in >70% of cases of T-ALL, including >85% or relapsed/ refractory disease, and only on a small fraction (<5%) of normal T cells. Using cell line models and patient-derived xenografts, we show chimeric antigen receptor (CAR)-T cells targeting CCR9 are resistant to fratricide and have potent anti-leukemic activity both in vitro and in vivo, even at low target antigen density. We propose anti-CCR9 CAR-T cells could be a highly effective treatment strategy for T-ALL, avoiding T cell aplasia and the need for genome engineering that complicate other approaches.
Archive Staff Only
 |
View Item |
