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Aims: The purpose of this study was to design and manufacture CD19 chimeric antigen receptor (CAR)‐modified T cells for clinical use in Thailand, as a model for how this technology can be directly applied at individual institutions treating high‐risk leukemia patients. Methods: We constructed second‐generation CAR T cells expressing CD19 scFV‐CD28‐CD3ζ with different lengths of the spacer region: full, intermediate, and short length, by using a lentiviral vector. We wanted to determine whether the difference in length of the spacer would affect the cytotoxic potential of the CD19 CAR T cells against the leukemic cells. Results: We found that all constructs of CD19 CAR T cells exhibited a similar level of cytotoxicity against several human lymphoma and leukemia cell lines. For the clinical application, we chose the intermediate length spacer construct CD19 CAR T cells, hypothesizing that the highest transduction efficiency coupled with a slower initial proliferation in vitro might lead to effective leukemic cell kill, yet a lower probability for serious clinical side effects. We then tested the clinical efficacy of our CD19 CAR T cells in one patient with refractory/relapsed acute B‐cell lymphoblastic leukemia. This patient indeed had minimal clinical side effects after the CAR T‐cell infusion, and he remains in an unmaintained, ongoing complete remission 10+ months after his T‐cell treatment. Conclusion: Our CD19 CAR T cells demonstrated efficacies in acute lymphoblastic B‐cell leukemia, and will be used to establish an immunotherapeutic program for high‐risk B‐cell acute lymphoblastic leukemia in Thailand. We propose that this approach can be used as a model for how this new exciting technology can be applied directly at individual institutions that treat (a large number of) patients with high‐risk leukemia. [ABSTRACT FROM AUTHOR]

EBV-PTLDs affect as high as 20% of SCT recipients especially those with T-cell depleted grafts while high mortality rates were also noted. Adoptive allogeneic and autologous CTLs have a therapeutic potential in this setting. However, the process of expansion of these cells is tedious and time consuming in both allogeneic and autologous CTL generation. For the allogeneic SCT, another major obstacle is unavailability of donors especially in an unrelated SCT setting. The aim of the present study was therefore to investigate the efficacy of autologous CIK cells (CD3+ CD56+) against autologous EBV-LCLs from post-SCT pediatric patients. We could demonstrate that CIK cells can be generated within two wk and did show the significant cytotoxicity against autologous EBV-LCLs. CIK cells may provide a potent tool for use in post-transplantation adoptive immunotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Osteosarcoma with distant metastases at late stage has posed a challenge for novel therapeutic modalities. The application of cytokine-induced killer (CIK) cells to osteosarcoma constitutes a promising strategy. This approach had been studied in multiple myeloma and breast cancers, where CIK cells exhibited specific cytotoxicity toward malignant cells while sparing wild-type tissues. However, the consistency of CIK cell-induced anti-tumor cytotoxicity has not been thoroughly examined. We investigated whether autologous CIK cells could effectively induce cytolysis of cultured osteosarcoma cells. In addition to the observed CIK cell-induced osteosarcoma cytolysis, the pre-incubation of CIK cells with autologous dendritic cells pulsed with tumor’s total RNA further enhanced the tumor cytolysis to greater than 6-fold. The anti-tumor cytolysis was optimized in complete autologous setting, and was attenuated with allogeneic components. The advantage of the co-culture with RNA-pulsed DC was lost when high CIK cell density was employed for anti-tumor cytotoxic assay, but was maintained in purified CD3+CD56+ cells isolated from the CIK cells. This finding implied that CIK cells at limited cell density could induce effective osteosarcoma cytolysis with an aid from tumor antigen presentation on dendritic cell surface. [Copyright &y& Elsevier]