Stable engraftment, as well as graft versus host disease-free and relapse-free survival brought by the combination of CD7 targeted universal chimeric antigen receptor-T, and donor hemopoietic stem cells: Indication of a case report.

CD7 targeted CAR-T has demonstrated potential in the treatment of T cell malignancies but no study has been reported about its potential in the prophylaxis of GVHD in allo-HSCT. Here we reported a special case that a boy diagnosed with refractory acute T lymphoblastic leukemia (T-ALL) was treated with universal CD7 targeted CAR-T (CD7 UCAR-T) and parent-derived peripheral blood stem cells (PBSCs). Complete remission and full engraftment of donor was observed. In the later four months of follow-up, in the absence of any immunodepression treatment, no signs of GVHD were observed. This case initially demonstrates the potential of CD7 UCAR-T in the prophylaxis of GVHD.

Modified lentiviral globin gene therapy for pediatric ß0/ß0 transfusion-dependent ß-thalassemia: A single-center, single-arm pilot trial.

ß0/ß0 thalassemia is the most severe type of transfusion-dependent ß-thalassemia (TDT) and is still a challenge facing lentiviral gene therapy. Here, we report the interim analysis of a single-center, single-arm pilot trial (NCT05015920) evaluating the safety and efficacy of a ß-globin expression-optimized and insulator-engineered lentivirus-modified cell product (BD211) in ß0/ß0 TDT. Two female children were enrolled, infused with BD211, and followed up for an average of 25.5 months. Engraftment of genetically modified hematopoietic stem and progenitor cells was successful and sustained in both patients. No unexpected safety issues occurred during conditioning or after infusion. Both patients achieved transfusion independence for over 22 months. The treatment extended the lifespan of red blood cells by over 42 days. Single-cell DNA/RNA-sequencing analysis of the dynamic changes of gene-modified cells, transgene expression, and oncogene activation showed no notable adverse effects. Optimized lentiviral gene therapy may safely and effectively treat all ß-thalassemia.

CD7 targeted "off-the-shelf" CAR-T demonstrates robust in vivo expansion and high efficacy in the treatment of patients with relapsed and refractory T cell malignancies.

T-cell acute lymphoblastic leukemia (T-ALL) represents an area of highly unmet medical needs. Once relapsed, patients have limited treatment options and poor prognosis. T-ALL antigens such as CD7 is extensively expressed in normal T cells and natural killer (NK) cells, and extending the success of CAR-T therapy to T cell malignancies was challenged by CAR-T cell fratricide, high production cost, and potential product contaminations. GC027 is an "off-the-shelf" allogeneic CD7 targeted CAR-T therapeutic product for T cell malignancies. It demonstrated superior cell expansion and antileukemia efficacy in mouse xenograft model. In our previous study, we observed promising efficacy results in the first two relapsed and refractory(R/R) T-ALL patients treated with GC027. In the expanded study, 11 out of 12 patients had rapid eradication of T-lymphoblasts and reached complete response within 1-month after GC027 infusion. GC027 cells expanded quickly beginning at infusion and reached to peak around 5-10 days after infusion. For most patients with a response(9/11), GC027 could not be detected via flow cytometry or qPCR 4 weeks after infusion. One patient had progression free survival of >3 years. With manageable toxicity profile, GC027 demonstrated superior clinical efficacy to standard chemotherapy regimens in (R/R) T cell malignancies.

Study on Oil and Gas Amphiphilic Surfactants Promoting the Miscibility of CO2 and Crude Oil.

In order to cope with the global climate crisis, carbon capture, utilization, and storage are the key technologies to achieve carbon neutrality, and it is an elegant geological utilization method for the oil and gas industry to improve the recovery rate of crude oil by using CO2. However, in practical applications, the problem of low miscibility of CO2 and crude oil, resulting in low oil displacement efficiency, cannot be avoided. Thus, finding an appropriate method to increase the utilization rate of CO2 is a worth in-depth study. In light of this, this paper carries out the study on improving the CO2 flooding efficiency by using oil and gas amphiphilic surfactants. First of all, according to the molecular structure theory and the solubility experiment of surfactants in CO2, five kinds of surfactants and two kinds of additives with good performance of oil and gas were selected. Then, three experiments were conducted to explore the mechanism of the selected surfactants. The main mechanism of promoting the miscibility of CO2-crude oil is to reduce the interfacial tension of the oil and gas phases, followed by increasing the volume expansion of crude oil and reducing the viscosity of crude oil. Finally, through the slim tube displacement experiment, the oil displacement efficiency effect of adding the compound systems of SPO5/n-pentanol was simulated. The results show that the oil displacement efficiency is significantly higher than that of pure CO2 flooding, and the pressure of miscibility reduces at the same time. The selected reagents have a good effect of promoting miscibility. Therefore, this is an effective method to improve the geological utilization of CO2.

lncRNA TP73-AS1 Regulates miR-21/PTEN Axis to Affect Cell Proliferation in Acute Myeloid Leukemia.

Objective: TP73-AS1 has been reported as an overexpressed oncogenic lncRNA in several types of cancer. However, these analyses of The Cancer Genome Atlas data set revealed downregulation of TP73-AS1 in acute myeloid leukemia (AML). In this study, we aimed to study the molecular mechanism between TP73-AS1 and cell proliferation in AML. Methods: Bone marrow (BM) samples were obtained from 50 AML patients and 50 healthy controls. Cell transient transfections were performed to analyze gene interactions. Dual-luciferase reporter assay, quantitative polymerase chain reaction and Western blot were used to study the gene expressions. Cell proliferation was analyzed by CCK-8 method. Results: TP73-AS1 was confirmed to be downregulated in AML. TP73-AS1 was predicted to interact with miR-21, while overexpression of TP73-AS1 and miR-21 did not affect the expression of each other. Instead, overexpression of TP73-AS1 led to the upregulation of phosphatase and tensin homologue (PTEN), a downstream target of miR-21. Cell proliferation analysis showed that overexpression of TP73-AS1 and PTEN led to a decreased proliferation rate of AML cells. Overexpression of miR-21 played an opposite role and reduced the effects of overexpressing TP73-AS1 and PTEN. Conclusion: TP73-AS1 may regulate the miR-21/PTEN axis to affect cell proliferation in AML.

Eradication of T-ALL Cells by CD7-targeted Universal CAR-T Cells and Initial Test of Ruxolitinib-based CRS Management.

PURPOSE: Although chimeric antigen receptor T-cell (CAR-T) therapy development for B-cell malignancies has made significant progress in the last decade, broadening the success to treating T-cell acute lymphoblastic leukemia (T-ALL) has been limited. We conducted two clinical trials to verify the safety and efficacy of GC027, an "off-the-shelf" allogeneic CAR-T product targeting T-cell antigen, CD7. Here, we report 2 patients as case reports with relapsed/refractory T-ALL who were treated with GC027. PATIENTS AND METHODS: Both the trials reported here were open-label and single-arm. A single infusion of GC027 was given to each patient after preconditioning therapy. RESULT: Robust expansion of CAR-T cells along with rapid eradication of CD7+ T lymphoblasts were observed in the peripheral blood, bone marrow, and cerebrospinal fluid. Both patients achieved complete remission with no detectable minimal residual disease. At data cutoff, 30 September 2020, 1 of the 2 patients remains in ongoing remission for over 1 year after CAR T-cell infusion. Grade 3 cytokine release syndrome (CRS) occurred in both patients and was managed by a novel approach with a ruxolitinib-based CRS management. Ruxolitinib showed promising activity in a preclinical study conducted at our center. No graft-versus-host disease was observed. CONCLUSIONS: The two case reports demonstrate that a standalone therapy with this novel CD7-targeted "off-the-shelf" allogeneic CAR-T therapy may provide deep and durable responses in select patients with relapsed/refractory T-ALL. GC027 might have a potential to be a promising new approach for treating refractory/relapsed T-ALL. Further studies are warranted.

LncRNA SNHG4 regulates miR-10a/PTEN to inhibit the proliferation of acute myeloid leukemia cells.

ABSTRACTObjectives: Long non-coding RNA (lncRNA) small nucleolar RNA host gene 4 (SNHG4) is a characterized oncogenic lncRNA in osteosarcoma. The analysis of the TCGA dataset suggested the downregulation of SNHG4 in acute myeloid leukemia (AML), indicating its possible involvement in this disease. Therefore, this study was performed to analyze the interaction between SNHG4 and miR-10a in AML.Methods: We included 60 patients with AML and 60 healthy participants. Transient transfections, luciferase activity assay, RT-qPCR, CCK-8, and Western blot were used to carry out the research.Results: In this study, we found that SNHG4 was downregulated in AML patients compared to healthy participants. SNHG4 and miR-10a can interact with each other. However, overexpression of SNHG4 and miR-10a failed to affect the expression of each other. Instead, SNHG4 overexpression led to upregulated PTEN, a downstream target of miR-10a. Cell proliferation analysis showed that SNHG4 and PTEN overexpression led to decreased proliferation rates of AML cells and attenuated the enhancing effects of miR-10a on cell proliferation.Conclusion: In conclusion, SNHG4 may regulate miR-10a/PTEN to inhibit the proliferation of AML cells.