Anti-CCR9 chimeric antigen receptor T cells for T-cell acute lymphoblastic leukemia

Paul M. Maciocia, Patrycja A. Wawrzyniecka, Nicola C. Maciocia, Amy Burley, Thaneswari Karpanasamy, Sam Devereaux, Malika Hoekx, David O'Connor, Theresa Leon, Tanya Rapoz-D'Silva, Rachael Pocock, Sunniyat Rahman, Giuseppe Gritti, Diana C. Yánez, Susan Ross, Tessa Crompton, Owen Williams, Lydia Lee, Martin A. Pule, Marc R. Mansour

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

25 Citas (Scopus)

Resumen

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of immature T lymphocytes, associated with higher rates of induction failure compared with those in B cell acute lymphoblastic leukemia. The potent immunotherapeutic approaches applied in B cell acute lymphoblastic leukemia, 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 show that the chemokine receptor CCR9 is expressed in >70% of cases of T-ALL, including >85% of relapsed/refractory disease, and only on a small fraction (<5%) of normal T cells. Using cell line models and patient-derived xenografts, we found that chimeric antigen receptor (CAR) T-cells targeting CCR9 are resistant to fratricide and have potent antileukemic activity both in vitro and in vivo, even at low target antigen density. We propose that 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.

Idioma originalInglés
Páginas (desde-hasta)25-37
Número de páginas13
PublicaciónBlood
Volumen140
N.º1
DOI
EstadoPublicada - 7 jul. 2022
Publicado de forma externa

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