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Novel anti-somatostatin receptor 2 antibody-drug conjugate for neuroendocrine cancer therapy

biorxiv. 2019; 
Yingnan Si,  Seulhee Kim,  Rachael Guenter,  Jianfa Ou,  Yun Lu,  Kai Chen,  John Zhang,  Jason Whitt,  Angela M. Carter,  James A. Bibb,  Renata Jaskula-Sztul,  James M. Markert,  Lufang Zhou,  Herbert Chen,  Xiaoguang “Margaret” Liu
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Gene Synthesis An isotype analysis revealed that the lead clone is IgG1 kappa, and SDS-PAGE analysis confirmed its molecular weight of 150 kDa (Fig. 3C). Further evaluation showed that the anti-SSTR2 mAb had high surface binding to NET cell lines BON-1 and QGP-1 (>90%) and low binding to fibroblast cell lines 917 and WI-38 (<7.5%) (Fig. 3D). Additionally, we and GenScript isolated, cloned and sequenced the mAb, and confirmed the novelty of our anti-SSTR2 mAb (PCT patent TH Docket No. 222119-8030). To optimally produce mAb, we adapted the adherent hybridoma cells to suspensive culture in stirred-tank bioreactor (Fig. 3E). The cultures in T-flask, spinner flask, and stirred-tank bioreactor generated 8.6, 39.8, and 53.3 mg/L of anti-SSTR2 mAb with a specific growth rate of 0.016, 0.024 and 0.035 hr−1, respectively (Fig. 3F). Get A Quote

摘要

Neuroendocrine (NE) cancers include a diverse spectrum of hormone-secreting neoplasms that arise from the endocrine and nervous systems. Current chemo- and radio- therapies have marginal curative benefits. This study aimed to develop an innovative antibody-drug conjugate (ADC) to effectively treat NE tumors (NETs). We first confirmed that somatostatin receptor 2 (SSTR2) is an ideal surface target by analyzing 38 patient-derived NET tissues, 33 normal organs, and 3 NET cell lines. We then developed a new monoclonal antibody (mAb, IgG1 and kappa) to target two extracellular domains of SSTR2, which showed strong and specific surface binding to NETs. The ADC was constructed by conjugating the anti-SSTR2 mAb and ant... More

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