Yi Xiao

B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies have shown efficacy in relapsed/refractory multiple myeloma (RRMM). Because the non-human originated antigen-targeting domain may limit clinical efficacy, we developed a fully human BCMA-specific CAR, CT103A, and report its safety and efficacy in a phase 1 trial. Eighteen consecutive patients with RRMM, including 4 with prior murine BCMA CAR exposures, were enrolled. CT103A was administered at 1, 3, and 6 × 106 CAR-positive T cells/kg in the dose-escalation phase, and 1 × 106 CAR-positive T cells/kg in the expansion cohort. The overall response rate was 100%, with 72.2% of the patients achieving complete response or stringent complete response. For the 4 murine BCMA CAR-exposed patients, 3 achieved stringent complete response, and 1 achieved a very good partial response. At 1 year, the progression-free survival rate was 58.3% for all cohorts and 79.1% for the patients without extramedullary myeloma. Hematologic toxicities were the most common adverse events; 70.6% of the patients experienced grade 1 or 2 cytokine release syndromes. No immune effector cell-associated neurotoxicity syndrome was observed. To the cutoff date, CAR transgenes were detectable in 77.8% of the patients. The median CAR transgene persistence was 307.5 days. Only 1 patient was positive for the anti-drug antibody. Altogether, CT103A is safe and highly active in patients with RRMM and can be developed as a promising therapy for RRMM. Patients who relapsed from prior murine BCMA CAR T-cell therapy may still benefit from CT103A. This trial was registered at http://www.chictr.org.cn as #ChiCTR1800018137.

OBJECTIVE: To design a simple model to assess the effectiveness of measures to prevent the spread of coronavirus disease 2019 (COVID-19) to different regions of mainland China. METHODS: We extracted data on population movements from an internet company data set and the numbers of confirmed cases of COVID-19 from government sources. On 23 January 2020 all travel in and out of the city of Wuhan was prohibited to control the spread of the disease. We modelled two key factors affecting the cumulative number of COVID-19 cases in regions outside Wuhan by 1 March 2020: (i) the total the number of people leaving Wuhan during 20-26 January 2020; and (ii) the number of seed cases from Wuhan before 19 January 2020, represented by the cumulative number of confirmed cases on 29 January 2020. We constructed a regression model to predict the cumulative number of cases in non-Wuhan regions in three assumed epidemic control scenarios. FINDINGS: Delaying the start date of control measures by only 3 days would have increased the estimated 30 699 confirmed cases of COVID-19 by 1 March 2020 in regions outside Wuhan by 34.6% (to 41 330 people). Advancing controls by 3 days would reduce infections by 30.8% (to 21 235 people) with basic control measures or 48.6% (to 15 796 people) with strict control measures. Based on standard residual values from the model, we were able to rank regions which were most effective in controlling the epidemic. CONCLUSION: The control measures in Wuhan combined with nationwide traffic restrictions and self-isolation reduced the ongoing spread of COVID-19 across China.

Abstract A new nonlinear optical (NLO) oxysulfide, Sr 6 Cd 2 Sb 6 O 7 S 10 , which contains the functional groups [SbO x S 5− x ] 7− ( x =0, 1) with a 5s 2 electron configuration, is synthesized by a solid‐state reaction. This compound displays a phase‐matchable second harmonic generation (SHG) response four times stronger than AgGaS 2 (AGS) under laser irradiation at 2.09 μm. Single‐crystal‐based optical measurements reveal a SHG intensity that can be tuned by temperature and novel photoluminescence properties. Theoretical analyses demonstrate that tetragonal [SbOS 4 ] 7− and [SbS 5 ] 7− pyramids make the predominant contribution to the enhanced SHG effect. Among those, the [SbOS 4 ] 7− units with mixed anions make a larger contribution. This work proposes that oxysulfide groups with an n s 2 electron configuration can serve as new functional building units in NLO materials and opens a new avenue for the design of other optoelectronic materials.

BACKGROUND: Chimeric antigen receptor-modified (CAR) T-cell immunotherapy is a novel promising therapy for treatment of B-cell malignancy. Cytokine release syndrome (CRS) and infection are the most common adverse events during CAR T-cell therapy. Similar clinical presentation of concurrent CRS and infection makes it difficult to differentially diagnose and timely treat the condition. METHODS: We analyzed the features of infection events during the first 30 days after CAR T-cell infusion (CTI) in 109 patients from three clinical trials (ChiCTR-OPN-16008526, ChiCTR-OPC-16009113, ChiCTR-OPN-16009847). Based on the dynamic changes of interleukin (IL)-6 and ferritin, we proposed the "double peaks of IL-6" pattern as a feature of life-threatening infection during the first 30 days after CTI. Meanwhile, we screened candidate biomarkers from 70-biomarker panel to establish a prediction model for life-threatening infection. RESULTS: In this study, 19 patients (17.4%) experienced a total of 19 infection events during the first 30 days after CAR T-cell infusion. Eleven patients (10.1%) had grade 4-5 infection, which were all bacterial infection and predominantly sepsis (N = 9). "Double peaks of IL-6" appeared in 9 out of 11 patients with life-threatening infection. The prediction model of three-cytokines (IL-8, IL-1β and interferon-γ) could predict life-threatening infection with high sensitivity (training: 100.0%; validation: 100.0%) and specificity (training: 97.6%; validation: 82.8%). On base of the aforementioned methods, we proposed a workflow for quick identification of life-threatening infection during CAR T-cell therapy. CONCLUSIONS: In this study, we worked out two diagnostic methods for life-threatening infection during CAR T-cell therapy by analyzing inflammatory signatures, which contributed to reducing risks of infection-induced death.