Humanized monoclonal antibodies (mAbs) against HER2 including trastuzumab and pertuzumab are widely used to treat HER2 overexpressing metastatic breast cancers. These two mAbs recognize distinct epitopes on HER2 and their combination induces a more potent blockade of HER2 signaling than trastuzumab alone. Recently, we have reported characterization of a new chimeric mAb (c-1T0) which binds to an epitope different from that recognized by trastuzumab and significantly inhibits proliferation of HER2 overexpressing tumor cells. Here, we describe humanization of this mAb by grafting all six complementarity determining regions (CDRs) onto human variable germline genes. Humanized VH and VL sequences were synthesized and ligated to human γ1 and κ constant region genes using splice overlap extension (SOE) PCR. Subsequently, the humanized antibody designated hersintuzumab was expressed and characterized by ELISA, Western blot and flow cytometry. The purified humanized mAb binds to recombinant HER2 and HER2-overexpressing tumor cells with an affinity comparable with the chimeric and parental mouse mAbs. It recognizes an epitope distinct from those recognized by trastuzumab and pertuzumab. Binding of hersintuzumab to HER2 overexpressing tumor cells induces G1 cell cycle arrest, inhibition of ERK and AKT signaling pathways and growth inhibition. Moreover, hersintuzumab could induce antibody-dependent cell cytotoxicity (ADCC) on BT-474 cells. This new humanized mAb is a potentially valuable tool for single or combination breast cancer therapy.

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This study presents a comprehensive systematic review and meta-analysis of randomized controlled trials (RCTs) on Chlorella vulgaris ( C. vulgaris ) supplementation and liver function biomarkers. Pertinent studies were identified using Scopus, ISI Web of Science, PubMed, and Cochrane library databases up to August 2020. Mean differences were pooled using a random-effects model. Pooling 7 RCTs together showed that C. vulgaris supplementation led to a significant reduction of serum aspartate aminotransferase (AST) levels (weighted mean difference [WMD], −9.15 U/L; 95% confidence interval [CI], −16.09, −2.21), but not alanine aminotransferase (ALT) or alkaline phosphatase (ALP) levels compared to the placebo consumption. Subgroup-analysis indicated that C. vulgaris supplementation had more effect on AST decreasing among non-alcoholic fatty liver disease patients (WMD, −16.42 U/L; 95% CI, −29.75, −3.09) than others. Furthermore, subgroup analysis based on kind of compression showed that C. vulgaris supplementation significantly decreased ALT levels (WMD, −4.65 U/L; 95% CI, −8.88, −0.42) compared with the placebo, but not metformin consumption. It seems that C. vulgaris supplementation mainly affects AST levels rather than ALT and ALP levels, however, as mentioned the effect of C. vulgaris on those enzymes might be context-dependent. Therefore, further investigations with a large number of patients as well as on different disorders are necessary and can provide more definitive evidence.