High efficacy and safety of low-dose CD19-directed CAR-T cell therapy in 51 refractory or relapsed B acute lymphoblastic leukemia patients.

Refractory or relapsed B lymphoblastic leukemia (B-ALL) patients have a dismal outcome with current therapy. We treated 42 primary refractory/hematological relapsed (R/R) and 9 refractory minimal residual disease by flow cytometry (FCM-MRD+) B-ALL patients with optimized second generation CD19-directed CAR-T cells. The CAR-T-cell infusion dosages were initially ranged from 0.05 to 14 × 105/kg and were eventually settled at 1 × 105/kg for the most recent 20 cases. 36/40 (90%) evaluated R/R patients achieved complete remission (CR) or CR with incomplete count recovery (CRi), and 9/9 (100%) FCM-MRD+ patients achieved MRD-. All of the most recent 20 patients achieved CR/CRi. Most cases only experienced mild to moderate CRS. 8/51 cases had seizures that were relieved by early intervention. Twenty three of twenty seven CR/CRi patients bridged to allogeneic hematopoietic stem cell transplantation (allo-HCT) remained in MRD- with a median follow-up time of 206 (45-427) days, whereas 9 of 18 CR/CRi patients without allo-HCT relapsed. Our results indicate that a low CAR-T-cell dosage of 1 × 105/kg, is effective and safe for treating refractory or relapsed B-ALL, and subsequent allo-HCT could further reduce the relapse rate.

Soluble BAFF-R produced by decidual stromal cells plays an inhibitory role in monocytes and macrophages.

A sophisticated immunological regulation between decidual stromal cells (DSC) and monocytes and macrophages is essential for the successful symbiosis of the mother and her fetus, but the mechanisms remain incompletely understood. The mRNA and proteins of B lymphocyte stimulator (BAFF, also known as BLys) and its receptor, BAFF-R (also known as BR3, CD268 or TNFRSF17), have been detected in both first-trimester and term placentas, but whether BAFF or BAFF-R participates in the cross-talk between DSC and monocytes and macrophages in the first-trimester pregnancy has not been described. This study found that purified DSC extensively shed BAFF-R and that polyinosinic:polycytidylic acid (poly(I:C); a synthetic toll-like receptor (TLR) 3 agonist) dramatically up-regulated BAFF-R secretion, suggesting that release of these soluble proteins was an inherent property of DSC and its induction might have relevance to TLR-3-mediated signal transduction. When monocytes were cultured with the supernatants of resting DSC or poly(I:C)-treated DSC, the proliferation of CD14(+)HLA-DR(+) monocytes (P=0.025 and 0.045) and the secretion levels of tumour necrosis factor α (P=0.035 and 0.031) and interleukin 6 (P=0.021 and 0.035) were significantly increased after the BAFF-R was blocked. Soluble BAFF-R may play inhibitory roles in monocytes and macrophages.

Establishment of serum protein pattern for screening colorectal cancer using SELDI-TOF-MS.

AIM: The purpose of this study is to develop a proteomic pattern for distinguishing individuals with colorectal cancer from healthy controls and monitoring micrometastasis using SELDI-TOF-MS. METHODS: A training set consisting of 63 patients with colorectal cancer, 20 patients with benign colorectal diseases and 26 healthy volunteers was used to develop a proteomic model that discriminated colorectal cancer effectively. The sensitivity and specificity of this model was validated by an independent test set. To explore serum proteins changed after operation, the protein profiles of 31 postoperative patients were compared with those of preoperative patients. We also analyzed protein profiles of patients with and without metastasis to monitor micrometastasis. RESULTS: Our study yielded a four-peak model (m/z: 3191.5, 3262.9, 3396.3 and 5334.4) that discriminated cancer from non-cancer samples with sensitivity of 90.3% and specificity of 95.7%. This model was validated in the test set with sensitivity of 87.5% and specificity of 93.8% which was significantly better than the combination use of CEA, CA199 and CA242 (sensitivity 62.4%) for early detection of colorectal cancer. Two peaks (m/z: 2753.8 and 4172.4) were found down-regulated in postoperative samples comparing with preoperative samples. We also detected two proteins (m/z: 9184.4 and 9340.9) that can discriminate patients with primary colorectal cancer from metastatic colorectal cancer. CONCLUSIONS: The four-peak model and two peaks (m/z: 2753.8 and 4172.4) detected in this study have the potential for assistance in diagnostics and therapeutic strategies in colorectal cancer and the two proteins (m/z: 9184.4 and 9340.9) were effective biomarkers for monitoring micrometastasis.