Risk factors for CAR-T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan

CAR-T細胞製造を成功させるためのレシピ --アフェレーシス前の下ごしらえでの工夫--. 京都大学プレスリリース. 2023-04-27.For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 × 10⁴/μL; p = 0.01) and CD4/CD8 T-cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for ≥6 cycles with washout period of 3–24 months; OR, 57.09; p = 0.005 for ≥3 cycles with washout period of <3 months), low platelet counts (OR, 0.495 per 105/μL; p = 0.022) or low CD4/CD8 ratios (<one third) (OR, 3.249; p = 0.011) in peripheral blood at apheresis increased the risk of manufacturing failure. Manufacturing failure remains an obstacle to CAR-T cell therapy for DLBCL patients. Avoiding risk factors, such as repeated bendamustine administration without sufficient washout, and risk-adapted strategies may help to optimize CAR-T cell therapy for DLBCL patients

Abnormal phospholipids distribution in the prefrontal cortex from a patient with schizophrenia revealed by matrix-assisted laser desorption/ionization imaging mass spectrometry

Schizophrenia is one of the major psychiatric disorders, and lipids have focused on the important roles in this disorder. In fact, lipids related to various functions in the brain. Previous studies have indicated that phospholipids, particularly ones containing polyunsaturated fatty acyl residues, are deficient in postmortem brains from patients with schizophrenia. However, due to the difficulties in handling human postmortem brains, particularly the large size and complex structures of the human brain, there is little agreement regarding the qualitative and quantitative abnormalities of phospholipids in brains from patients with schizophrenia, particularly if corresponding brain regions are not used. In this study, to overcome these problems, we employed matrix-assisted laser desorption/ionization imaging mass spectrometry (IMS), enabling direct microregion analysis of phospholipids in the postmortem brain of a patient with schizophrenia via brain sections prepared on glass slides. With integration of traditional histochemical examination, we could analyze regions of interest in the brain at the micrometric level. We found abnormal phospholipid distributions within internal brain structures, namely, the frontal cortex and occipital cortex. IMS revealed abnormal distributions of phosphatidylcholine molecular species particularly in the cortical layer of frontal cortex region. In addition, the combined use of liquid chromatography/electrospray ionization tandem mass spectrometry strengthened the capability for identification of numerous lipid molecular species. Our results are expected to further elucidate various metabolic processes in the neural system

Pitfalls and practicalities in collecting and banking human brain tissues for research on psychiatric and neulogical disorders

It is essential to examine brain materials for the understanding the cause and pathology of mental disorders. Recent methodological progress urges us to set up well qualified brain banks. Human tissue and Bio-banking is a complex field and the daily practice of brain banks needs to abide by several golden standards in order to avoid pitfalls in basic research: 1) A donor system in which informed consent is granted for the use of the samples for scientific research, including genetic analysis and access to medical records, 2) Rapid autopsy system, 3) Compatibility of protocols for procurement, management, handling and storage, 4) A generally accepted consensus on diagnostic criteria, 5) Quality control, 6) Abiding by local/international legal and ethical guidelines for work with human material, 7) Proper safety procedures. In the present review, the authors introduced the activities of European brain banks, and discussed on their current issues, and on the problems remain to be resolved

Nutritional Properties and Processing Characteristics of Akebia quinata

Akebia quinata is a naturally edible fruit and its seeds have been used as materials for edible oil at Akita Prefecture in Japan. However it is not well recognized to consumers owing to the limited information for nutritional properties and cooking method. Particularly its pericarp has not been utilized because of its bitter taste although it contains several functional ingredients such as antioxidants. In the present studies we developed the processing method of the pericarp of Akebia quinata to reduce bitter tastes. We also made new cooking methods and their availabilities were investigated in the lecture class for general citizens. The usability of Akebia quinata as health food materials was discussed to promote the consumption of the regional food resources

Nutritional Cooking Characteristics of Akebia Seed Oil and Evaluation as a Dressing Material

Akebia seed oil is traditional edible oil produced in Akita prefecture, Japan. However, it is not well recognized to consumers owing to the limited information for physicochemical properties and processing methods. In the present studies we evaluated acid value (AV), peroxide value (POV), viscosity, and color tone of akebia seed oil and other plant oils. Akebia seed oil showed relatively higher AV and POV as compared with other vegetable oils owing to its unrefined process. It had a lower viscosity than other vegetable oils because of the difference in the main component, which of akebia seed oil was 1,2-diacylglycero-3-acetate (DAGA) whereas other vegetable oils mainly contained triacylglycerol (TG). The preferences of vegetable oil and dressing were investigated by sensory evaluation. Akebia seed oil and dressing showed relatively stronger bitterness, habit, and residual aftertaste than other vegetable oils. However, vegetable oils except akebia seed oil were industrially refined. It is necessary to consider how to use akebia seed oil by taking advantage of the characteristics of unrefined oil and refined oil. The usability of akebia seed oil as health food materials was also discussed

Utilization of Edible Wild Plant in Akita Prefecture and Comparison of Eating Experience of White Goosefoot (Chenopodium album) between Japan and Bangladesh

The edible wild plants were anciently important food materials as sources of nutrients such as vitamins but their utilization has been decreasing in the present day. To elucidate the utilization of edible wild plants in Akita prefecture of Japan, we performed questionary survey targeting at the inhabitants of the wide age age group. Elatostema umbellatum (“Mizu”), Osmunda japonica (Asian royal fern, "Zenmai") and Oenanthe javanica, (Java waterdropwort. “Seri”) were eaten well most. Laportea cuspidate (“Aiko”), Parasenecio hastatus (“Honna”) and Parasenecio delphiniifolius (“Shidoke”) were utilized well in Tohoku region and their rate of experiences of eating exceeded 70%. It is observed that Chenopodium album (white goosefoot, “Shiroza”) grows on the roadside in Japan, but 82.4% of the inhabitants did not know that they were edible. We also performed questionary survey in Bangladesh, where Chenopodium album is cultivated and eaten well. In our investigation, all Bangladeshi had the experiences of eating and it was used as a materials of the traditional cuisine such as sauteed vegetables, bhorta and curry. The values of Chenopodium album as foods in emergency and its availabilities as the teaching materials for safeguard against disaster were also discussed

Polyphenol contained in Edible Wild Plant in Akita Prefecture and Analysis of Physiological Function of White Goosefoot (Chenopodium album)

To estimate the physiological function of Chenopodium album (white goosefoot, “Shiroza”), polyphenol content and anti-oxidant activity were evaluated. Chenopodium album had higher amount of total polyphenol than the other edible wild plants in Akita prefecture and showed potent anti-oxidant activity compared with the other plants. Although the extract of Chenopodium album had a little anti-tumor activity against U937 cells, the water extract of Chenopodium album exhibited neuroprotective effects when Neuro-2a cells were treated with tunicamycin. It also suppressed adipocyte-differentiation of 3T3-L1 cells and decreased triglyceride accumulation. These results suggest that Chenopodium album has a potential for health food materials to prevent dementia and obesity-related diseases such as type II diabetes. The utilization of Chenopodium album as processed foods in healthy diet was also discussed