イオサイトジェンは腫瘍、腫瘍免疫、自己免疫疾患及び他の炎症疾患分野に集中し、遺伝子修飾ヒト化マウス、重度免疫欠陥B-NDGマウス及び一連の変更マウス、野生型マウスなどの構築した上で、高品質in vivo薬効サービスを提供しております。弊社は様々な新薬候補物質(生物製剤、モノクローナル抗体及び二重特異性抗体)、低分子化合物、CAR-Tなどの細胞治療薬物など)や各種併用療法の前臨床薬効の評価に対す豊富な経験を有しています。以下には一部研究事例を示しています。

HUMANIZED IMMUNE-CHECKPOINT SYNGENEIC MOUSE MODELS 

HUMANIZED CD3E-BASED BISPECIFIC ANTIBODY EFFICACY MODEL

HUMAN IMMUNE SYSTEM ENGRAFTED MOUSE MODEL

CAR-T EFFICACY EVALUATION MODELS  CDX MODELS 

生物製剤や低分子治療薬のin vivo薬効研究の詳しい情報に関しては、こちらをご覧ください。

免疫機能シンジェニックマウスモデルによる免疫チェックポイント抗体の薬効の評価

Check-point-Antibody-Efficacy

Murine colon cancer MC38 cells were subcutaneously implanted into homozygous B-hPD-1 mice, where the extracellular domain of human PD-1 replaces that of mouse PD-1 via genomic knock-in. Mice were grouped when the tumor size reached 150 ± 50 mm3 (n=10). The human PD-1 antibody pembrolizumab significantly inhibited tumor growth, confirming that the B-hPD-1 mouse model is a powerful tool for in vivo anti-human PD-1 efficacy studies. Tumor volume: mean ± SEM (A).  Body weight: mean ± SEM (B).

二重特異性抗体の薬効研究

Bispecific-Antibody-Efficacy-Study

Murine colon cancer cells MC38 engineered to express human CD19, MC38-hCD19, were subcutaneously implanted into B-hCD3e mice, where the extracellular domain of human CD3e replaces that of mouse CD3e via genomic knock-in. Mice were grouped (n=6) when the tumor sizes were approximately 150 ± 50 mm3. Blinatumomab, a bispecific antibody targeting human CD3e and human CD19, significantly inhibited tumor growth, demonstrating that the B-hCD3e mice are a powerful model for in vivo efficacy evaluation of anti-hCD3e-based bispecific antibodies. Tumor volume: mean ± SEM (A). Body weight: mean ± SEM (B).

低分子医薬品の薬効研究

低分子医薬品は重要な癌治療の薬です。バイオサイトジェンは低分子治療の薬効評価の豊富な経験を持ち、以下はサービスの実例です。

小分子功效研究

Murine colon cancer MC38-hPD-L1 cells were subcutaneously implanted into homozygous B-hPD-1 mice. Mice were grouped when the tumor size reached approximately 150 ± 50 mm3 (n=8). Combination of anti-hPD-1 antibody pembrolizumab and the chemotherapy drug cisplatin showed additional inhibitory effects on tumor growth than individual agents alone in B-hPD-1 mice. Tumor volume: mean ± SEM (A). Body weight: mean ± SEM (B).

重度免疫欠陥(B-NDG)マウスを用いてCAR-T細胞薬物のin vivo薬効の評価

CAR-T-Cell-Efficacy

Efficacy of various CAR-T therapy targeting human CD20 was evaluated in highly immune-deficient B-NDG mice inoculated with modified human B cell lymphoma cells, B-Raji-Luc-GFP.  Various CAR-T cells were injected i.v. at the same time of B-Raji-Luc-GFP cells. (A) Luciferase signals as an indicator of tumor load in mice treated with different CAR-T cells. (B) Body weight of treated mice. All values are expressed as mean ± SEM.

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