Characterization of a xenograft model for anti-CD19 CAR T cell studies

Purpose Chimeric antigen receptor (CAR) T cell development for B cell malignancies treatment has triggered a paradigm shift in oncology. The development of anti-CD19 CAR T cells relies primarily on a panel of cell line-derived xenograft models, including Raji cells; however, the behavior of this model is under debate. We attempted to characterize this lymphoma model and propose outcome measures for CAR T cell studies Methods Raji cell line was inoculated into NOG mice via intra-venous (IV), intra-peritoneal (IP), and subcutaneous (SC) routes with different inoculum sizes, and consequent clinical and histopathological outcomes were assessed. Results Inoculum sizes of 105–106 resulted in a complete take rate. The mice with IV and SC-inoculated Raji cells presented the shortest and longest survival among lymphoma-bearing mice, respectively (P < 0.01). The IP group had the highest number of both infiltrated organs (P < 0.05; compared to SC) and involvement of lymphatic sites (P < 0.05; compared to IV). The number of lymphoma lesions on the liver was higher in the IV compared to IP (P < 0.001) and SC (P < 0.05). Conclusion We demonstrate that the Raji cell line inoculation route could determine the xenograft model system behavior in terms of survival, tumor burden, and dissemination pattern and gives the model the specific features suitable for testing the specific hypothesis in CAR T cell therapy. We also conclude outcome measures for CAR T cell studies that do not require imaging techniques (AU)

Characterization of a xenograft model for anti-CD19 CAR T cell studies.

PURPOSE: Chimeric antigen receptor (CAR) T cell development for B cell malignancies treatment has triggered a paradigm shift in oncology. The development of anti-CD19 CAR T cells relies primarily on a panel of cell line-derived xenograft models, including Raji cells; however, the behavior of this model is under debate. We attempted to characterize this lymphoma model and propose outcome measures for CAR T cell studies METHODS: Raji cell line was inoculated into NOG mice via intra-venous (IV), intra-peritoneal (IP), and subcutaneous (SC) routes with different inoculum sizes, and consequent clinical and histopathological outcomes were assessed. RESULTS: Inoculum sizes of 105-106 resulted in a complete take rate. The mice with IV and SC-inoculated Raji cells presented the shortest and longest survival among lymphoma-bearing mice, respectively (P < 0.01). The IP group had the highest number of both infiltrated organs (P < 0.05; compared to SC) and involvement of lymphatic sites (P < 0.05; compared to IV). The number of lymphoma lesions on the liver was higher in the IV compared to IP (P < 0.001) and SC (P < 0.05). CONCLUSION: We demonstrate that the Raji cell line inoculation route could determine the xenograft model system behavior in terms of survival, tumor burden, and dissemination pattern and gives the model the specific features suitable for testing the specific hypothesis in CAR T cell therapy. We also conclude outcome measures for CAR T cell studies that do not require imaging techniques.

Knowledge and attitude of donor cardholders toward organ and tissue donation and transplantation in an Iranian tissue bank: a case-control study.

BACKGROUND: Cadaveric organ shortage is the most important obstacle to more widespread provision of transplants. Many factors influence the donation rate: social factors, religion, familial relations, and especially knowledge and attitudes toward organ and tissue donation and transplantation. Increasing public awareness can reform the incorrect beliefs and myths about donation and transplantation. This study investigated knowledge and attitudes of donor cardholders toward organ and tissue donation as well as transplantation. METHODS: This case-control study was performed in 2006 among 178 donor cardholders and the same number of a control group who completed a questionnaire including 23 questions and demographic information. FINDINGS: Knowledge and attitude among the cardholder was significantly greater than the control group (P < .05). We observed a inverse correlation between age and a positive attitude toward donation and transplantation among cardholders. CONCLUSION: This study suggested that the main reasons for refusal to donate organ and tissue were insufficient knowledge and negative attitudes due to misinformation regarding donation and transplantation. We believe that educating and motivating the public via the mass media can increase the rate of consent for organ and tissue donation and transplantation.

Comparative study of depression and consent among brain death families in donor and nondonor groups from March 2001 to December 2002 in Tehran.

OBJECTIVE: The aim of this research was to study the relationship between depression and organ donation among families of brain death cases. MATERIALS AND METHODS: This descriptive, cross-sectional study included a sample of first-degree relatives of brain death cases: 54 relatives among 27 organ donor families and 104 relatives among 58 nonorgan donor families participated in the research by the counting method. All families were questioned about their willingness for organ donation and at least 3 months had passed from their relative's death to the time we performed the research. Data were collected via a demographic questionnaire and Beck depression inventory (BDI) with a cutoff point of 16; persons with scores over 16 were considered depressed. Data were analyzed using descriptive statistics, Student t test, and chi-square test. RESULTS: Depression was observed in 20.4% of donor families and 17.3% of nondonor families; there was no significant difference between them. There were no significant differences in the frequency of depression between parents, spouses, and children of the 2 groups. The organ donors' relatives reported the effectiveness of organ donation to alleviate their grief: 66% completely and 32% partially. CONCLUSION: Organ donation does not have a significant effect on the course of grief and later depression among relatives of brain death cases.

Comparison of mirtazapine and fluoxetine in the treatment of major depressive disorder: a double-blind, randomized trial.

BACKGROUND: Depression is an international public health problem. The aim of this study was to compare the efficacy and tolerability of mirtazapine and fluoxetine treatment in a sample population consisting of Iranian patients suffering major depressive disorder. METHODS: Thirty-six inpatients and outpatients with a diagnosis of major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders-IV) and a score > or = 18 on the 17-item Hamilton Rating Scale for Depression (HAM-D-17) were randomly assigned to 6 weeks of treatment with mirtazapine (30 mg/day) or fluoxetine (20 mg/day). Efficacy was assessed by HAM-D-17. Information about adverse events was obtained by questioning of participants and/or their examination. Assessments were performed at weeks 0, 1, 2, 3, 4 and 6. RESULTS: Sixteen of mirtazapine-treated patients and fifteen of fluoxetine-treated patients completed the 6-week study period. Both treatment groups were well matched at baseline with respect to demographic and disease characteristics. Both drugs showed a significant improvement over the 6 weeks of treatment (P < 0.001). There was no statistically significant difference between the mean +/- SEM HAM-D scores of two groups at weeks 1, 2, 3, 4, and at the end point. There were no significant differences between two groups in terms of response to treatment (> or = 50% decrease from baseline in HAM-D-17 total score) and remission (HAM-D-17 score of < or = 7). None of the differences in reported adverse events was statistically significant. CONCLUSION: In this study, mirtazapine and fluoxetine were equally effective and well tolerated after 6 weeks of treatment in patients with major depressive disorder.