METHODS FOR THE TREATMENT OF ADULT T-CELL LEUKEMIA/LYMPHOMA

摘要

Adult T-cell leukemia/lymphoma (ATL) is an aggressive proliferation of mature activated CD4+ T cells associated with the human T-cell lymphotropic virus type I (HTLV-I). The inventors performed an integrated genomic analysis of a retrospective cohort of 62 ATL patients mainly originating from Africa and the Caribbean area. In particular, they identified a subset of mutations in the TCR/NF-KB pathway (PLCG1, CARD11, PRKCB, CBLB, IRF4, CSNK1A1, FYN, RHOA, VAV1). Furthermore, the inventors investigated the effects of an anti-CD3 antibody (OKT3) exposure on 4 ATL samples including 2 cases harboring CARD 11 and PRKCB gain of function alterations and 2 cases without any TCR pathway mutation. The data suggest that ATL harboring TCR pathway mutations clearly responded to anti-CD3 (Fig. IB, red + OKT3) and died by apoptosis possibly by a mechanism resembling AICD. Importantly, these TCR-pathway/NFKB mutated patients also showed poorer outcome as compared to unmutated cases. Accordingly, the present invention relates to a method of treating adult T-cell leukemia/lymphoma (ATL) in a patient in need thereof comprising administering to the patient a therapeutically effective amount of an anti-CD3 antibody.