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Philadelphia chromosome-positive acute lymphoblastic leukemia has a poor prognosis, even in pediatric patients. Although imatinib-containing chemotherapy can reportedly improve early event-free survival, allogeneic hematopoietic stem cell transplantation is still considered to be the main curative treatment option. Dasatinib, a novel abl tyrosine kinase inhibitor, is being used for the treatment of relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia and is reported to have excellent efficacy. We used dasatinib after bone marrow transplantation prior to the anticipated relapse for the purpose of prophylaxis against relapse. After discontinuation of dasatinib administration, molecular remission has lasted for 7 months. Although preventive use of dasatinib is as yet uncommon, we consider that dasatinib may eradicate the minimal residual disease and prevent recurrence, and it is feasible to administer and appears to be safe. Further studies are needed to confirm our experience in this case.

Objectives One of the reasons as to why chimeric antigen receptors (CAR)‐T cell therapy for malignancies other than CD19‐ or BCMA‐positive tumors has yet to produce remarkable progress is the paucity of targetable antigens. NKp44 is only expressed by activated natural killer cells and detects a variety of transformed cells, while it reportedly does not react with normal tissues. The aim of this study is to develop CAR‐T cell that can target multiple types of tumor cells. Methods We created a series of novel CAR constructs in first‐generation (1G) and second‐generation (2G) CAR format with the extracellular immunoglobulin‐like domain of NKp44 (NKp44‐CAR). Results Transduction of the best 1G construct into human primary T cells led to specific cytotoxic effects and cytokine secretion upon encountering multiple types of neoplastic cells including AML, T‐ALL and childhood solid tumors. Replacement of the extracellular hinge domain of NKp44 with that of CD8α resulted in diminished CAR function. The 1G NKp44‐CAR‐T cells exhibited significantly better tumor control in long‐term co‐culture assays compared with activated NK cells, as well as with NK cells transduced with identical NKp44‐CAR. T cells transduced with the best 2G‐CAR construct with 4‐1BB co‐stimulatory domain proliferated at significantly higher levels upon single antigen exposure and showed significantly better tumor control compared with the 1G‐CAR and 2G‐CAR with CD28 co‐stimulatory domain. Conclusions NKp44‐based CAR endows T cells with NK cell‐like anti‐tumor specificity. The CAR gene created in this study will be useful for the development of novel gene‐modified T‐cell immunotherapy.

Highlights P. acidilactici infection can be self-limiting, even in immunocompromised hosts. P. acidilactici infection can occur in dasatinib-induced hemorrhagic colitis. Dairy products consumers can cause P. acidilactici bacteremia.

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