T cell defects: new insights into the primary resistance factor to CD19/CD22 cocktail CAR T-cell immunotherapy in diffuse large B-cell lymphoma was written by Wang, Jiachen;Shen, Kefeng;Mu, Wei;Li, Weigang;Zhang, Meilan;Zhang, Wei;Li, Zhe;Ge, Tong;Zhu, Zhoujie;Zhang, Shangkun;Chen, Caixia;Xing, Shugang;Zhu, Li;Chen, Liting;Wang, Na;Huang, Liang;Li, Dengju;Xiao, Min;Zhou, Jianfeng. And the article was included in Frontiers in Immunology in 2022.COA of Formula: C16H21Cl2N3O2 The following contents are mentioned in the article:
Despite impressive progress, a significant portion of patients still experience primary or secondary resistance to chimeric antigen receptor (CAR) T-cell immunotherapy for relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). The mechanism of primary resistance involves T-cell extrinsic and intrinsic dysfunction. In the present study, a total of 135 patients of DLBCL treated with murine CD19/CD22 cocktail CAR T-therapy were assessed retrospectively. Based on four criteria (maximal expansion of the transgene/CAR-pos. T-cell levels post-infusion [Cmax], initial persistence of the transgene by the CAR transgene level at +3 mo [Tlast], CD19+ B-cell levels [B-cell recovery], and the initial response to CAR T-cell therapy), 48 patients were included in the research and divided into two groups (a T-normal group [n = 22] and a T-defect [n = 26] group). According to univariate and multivariate regression analyses, higher lactate dehydrogenase (LDH) levels before leukapheresis (hazard ratio (HR) = 1.922; p = 0.045) and lower cytokine release syndrome (CRS) grade after CAR T-cell infusion (HR = 0.150; p = 0.026) were independent risk factors of T-cell dysfunction. Moreover, using whole-exon sequencing, we found that germline variants in 47 genes were significantly enriched in the T-defect group compared to the T-normal group (96% vs. 41%; p<0.0001), these genes consisted of CAR structure genes (n = 3), T-cell signal 1 to signal 3 genes (n = 13), T cell immune regulation- and checkpoint-related genes (n = 9), cytokine- and chemokine-related genes (n = 13), and T-cell metabolism-related genes (n = 9). Heterozygous germline UNC13D mutations had the highest intergroup differences (26.9% vs. 0%; p = 0.008). Compound heterozygous CX3CR1I249/M280 variants, referred to as pathogenic and risk factors according to the ClinVar database, were enriched in the T-defect group (3 of 26). In summary, the clin. characteristics and T-cell immunodeficiency genetic features may help explain the underlying mechanism of treatment primary resistance and provide novel insights into CAR T-cell immunotherapy. This study involved multiple reactions and reactants, such as 4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7COA of Formula: C16H21Cl2N3O2).
4-(5-(Bis(2-chloroethyl)amino)-1-methyl-1H-benzo[d]imidazol-2-yl)butanoic acid (cas: 16506-27-7) belongs to imidazole derivatives. Many natural products, especially alkaloids, contain the imidazole ring. These imidazoles share the 1,3-C3N2 ring but feature varied substituents. Imidazole derivatives have antibacterial, antifungal and anticancer functionality. It interacts with DNA and also binds to protein and stops cell division.COA of Formula: C16H21Cl2N3O2
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem