Academic literature on the topic 'Shi long chang you qi tian'

Abstract Acute lymphocytic leukemia (ALL) is the most common form of leukemia in childhood and adolescence. Outcomes of relapsed/refractory adult B-ALL remain dismal with long-term survival of less than 10%. Although targeted therapies such as blinatumomab, inotuzumab ozogamicin, and CD19 CAR T cell therapy are a significant treatment advance for patients with B-ALL, there is still an unmet medical need for novel therapies for B-ALL. CRLF2-rearranged B-ALL, a subtype of Philadelphia chromosome-like B-ALL, is a high-risk disease subset with poor long-term outcomes. In an effort to identify new therapeutic targets for B-ALL, we validated by flow cytometry that patients with CRLF2-rearranged Ph-like ALL overexpress thymic stromal lymphopoietin receptor (TSLPR) at levels comparable with CD19. We subsequently generated antibodies against TSLPR from immunized H2L2 Harbor mice through single B cell cloning technology. The lead antibody was further engineered to a CD3-redirecting bispecific antibody (BsAb) using Xencor’s CD3e bispecific antibody technology to create 1B7/CD3 BsAb with an Fc-silent region. 1B7/CD3 BsAb exhibits high affinity binding to both human and cynomolgus monkey CD3e and TSLPR by BLI. Additionally, UHPLC-SEC analysis of 1B7/CD3 shows that this BsAb is stable without any aggregation or degradation present after five weeks incubation at 37 °C. In cell-based analyses,1B7/CD3 BsAb demonstrate potent antigen-specific T cell activation and tumor lysis activity against TSLPR+-REH and MHH-CALL4 cell lines as well as a primary B-ALL patient sample, but none against human peripheral blood mononuclear cells (PBMC) collected from healthy donors. Animal tumor models suggest that 1B7/CD3 triggers a dose-dependent tumor regression or growth inhibition in PBMC humanized TSLPR-REH CDX and BOS-1 PDX models across donors. Correspondingly, T cell activation and expansion were examined by CD69 and CD3+ T cells with the best effect observed at the 1mg/kg dose. 1B7/CD3 exhibits durable PK with T1/2 in NSG mice of up to ten days. Finally, 1B7/CD3 BsAb demonstrated a tolerable safety margin in a two-dose exploratory toxicity study in cynomolgus monkeys with MTD equal to or less than 1mg/kg. Consistent with clinical observation, we observed a transient increase of six major cytokines (IFNγ, IL-6, IL-8, IL-10, MCP-1 and TNFα) 4hr post the initial dosing, but no notable induction of cytokine levels after the second dosing (except for IL-8). Thus, our preclinical data provide the framework for the clinical evaluation of 1B7/CD3 BsAb in patients with CRLF2-rearranged B-ALL. Citation Format: Ze Tian, chunhua shi, Amin AI-Shami, GuoJun Yong, Jason K Allen, Jill Wardell Olson, Melinda G Smith, Qing Chang, Qing Shi, Junping You, Michelle A Gonzalez, Timothy E Lofton, Jasbir Kaur, Qi Zhang, DongXing Zha, Nitin Jain, Marina Y Konopleva, Timothy Heffernan, Jeffrey J Molldrem. preclinical development of a novel anti-tslpr bispecific antibody 1b7/cd3 targeting crlf2-rearranged ph-like b-all. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5655.

Aims: Fokienia hodginsii is a threatened conifer tree species, known as the dominant nursery-grown species capable of colonizing the challenging woodland environments in southern China due to its strong root penetrating ability. The ecological phenotype of Fokienia hodginsii is not well documented during its breeding process, which limits the potential planting area and its ecological function. This study aims to understand how Fokienia hodginsii associates with microbes to conduct its key ecological function and provide a theoretical basis for further improving the forest nursery management of Fokienia hodginsii. Methods: This study explored the ecological traits of 11 main Fokienia hodginsii provenances in a homogeneous garden experiment by analyzing their nutrient utilization strategies and associated microbial features in the rhizosphere soil and roots. Results: The study found that the paramount difference in the rhizosphere soil among provenances is in Ca and Fe content. Some microbial communities, namely Crenarchaeota, Verrucomicrobiota, and Desulfobacterota, were positively correlated with the amounts of the soil nutrient elements, whereas Abditibacteriota and Dependentiae were negatively correlated. The abundance of N- and Fe-related bacteria in the Fu Jian Chang Ting (FJCT) provenance was significantly higher than that in other provenances, while the C-, P-, K-, and Mg-related fungal communities, respectively, had higher abundances in the FJCT, Fu Jian Long Yan (FJLY), Fu Jian Gu Tian (FJGT), and Fu Jian Xian You (FJXY) provenances than the others. The impacts of the Gui Zhou Li Ping (GZLP), Hu Nan Dao Xian (HNDX), Jiang Xi Shang Yao (JXSY), and Guang Dong Shi Xing (GDSX) provenances on the rhizosphere soil are similar, but the differences in nutrient utilization arise from the plant itself. Conversely, the root nutrient contents of the FJCT, Fu Jian You Xi (FJYX), Fu Jian An Xi (FJAX), FJLY, Fu Jian De Hua (FJDH), FJGT, and FJXY provenances are highly correlated with soil nutrient features. Conclusions: For the native provenances, their economic traits are better than the exotic provenances. The native provenances are more sensitive to local soil conditions, so they should benefit more from human interventions, rendering them more suitable for artificial cultivation. The growth of the exotic provenances is less affected by the soil environment, making them better suited for the ecological transformation of forest stands and soil improvement.