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產(chǎn)品與研發(fā)

研制創(chuàng)新藥物捍衛(wèi)人類(lèi)健康

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關(guān)于TGF-β

轉(zhuǎn)化生長(zhǎng)因子-β（transforming growth factor-β, TGF-β）是屬于一組調(diào)節(jié)細(xì)胞生長(zhǎng)和分化的TGF-β超家族，主要有TGF-β1、TGF-β2、TGF-β3三個(gè)亞型，研究顯示各TGF-β亞型在腫瘤的發(fā)生發(fā)展中發(fā)揮著重要作用，如：（1）抑制免疫活性細(xì)胞的增殖；（2）抑制淋巴細(xì)胞的分化；（3）抑制細(xì)胞因子產(chǎn)生：如抑制PBMC中IFN-γ和TNF-α的產(chǎn)生；（4）其它調(diào)節(jié)作用：①促進(jìn)成纖維細(xì)胞、成骨細(xì)胞的生長(zhǎng)；②抑制上皮細(xì)胞、破骨細(xì)胞、內(nèi)皮細(xì)胞生長(zhǎng)和脂肪、心肌、骨骼肌的形成；③促進(jìn)細(xì)胞外基質(zhì)（ECM）如膠原蛋白、纖粘連蛋白的表達(dá)和抑制ECM的降解，對(duì)細(xì)胞的形態(tài)發(fā)生、增殖和分化過(guò)程起著重要作用，有利于胚胎發(fā)育和細(xì)胞修復(fù)；④單核細(xì)胞和成纖維細(xì)胞的趨化劑；⑤抑制淋巴細(xì)胞與內(nèi)皮細(xì)胞的黏附；⑥促進(jìn)嗜堿性粒細(xì)胞釋放組織胺。較高水平的TGF-β與晚期惡性腫瘤的免疫逃逸、治療抵抗（化療、放療、檢查點(diǎn)抑制劑）和不良預(yù)后相關(guān)，目前全球有多個(gè)針對(duì)TGF-β通路的小分子抑制劑和單克隆抗體藥物臨床在研，如諾華TGF-β單抗NIS793以及M7824、SHR1701等PD-L1×TGF-β雙功能抗體融合蛋白在部分臨床研究中已經(jīng)顯示出抗TGF-β對(duì)療效的增加，但尚無(wú)上市TGF-β抗體類(lèi)藥物。

參考文獻(xiàn)

The bispecificantibody blocked TGF-β and PD-L1 pathways and had a superior anti-tumor effect compared to the monotherapies；

Combining Mn2+ with anti-PD-L1xanti-TGF-β bsAb has a synergistic antitumor effect, effectively controlling tumor growth and prolonging the survival of tumor-bearing mice. This novel cocktail strategy has the potential to be a universal regimen for inflamed and non-inflamed tumors.

MSA-2 synergizes with anti-PD-L1xanti-TGF-β bsAb in boosting antitumor immunity. This immune cocktail therapy effectively overcomes immunotherapy resistance in immune-excluded and immune-desert models.