EpCAM CAR-T臨床試驗具有極高風險請患者小心

我其實不太了解為什麼中國的醫生會挑選EpCAM這個分子作為CART細胞的攻擊靶向分子,因為這個分子在大多數正常組織的上皮細胞都有表達,完全沒有道理。 文獻中早就說過了,我給出一篇作為例子。

Front Biosci. 2008 Jan 1;13:3096-100.

EpCAM expression in normal, non-pathological tissues.

Schmelzer E1, Reid LM.

Author information

Abstract

Epithelial Cell Adhesion Molecule (EpCAM) is a transmembrane glycoprotein that is associated with various cancers. Most normal, non-pathological epithelial tissue is EpCAM positive with the exception of epidermal keratinocytes, gastric parietal cells, myoepithelial cells, thymic cortical epithelial, and hepatocytes. However, during early liver development EpCAM expression is also observed. In our studies, we have demonstrated that EpCAM is expressed in non-pathological human livers on hepatic progenitors in livers of all donor ages, from 16 weeks gestation fetal livers to adult. Hepatic progenitors of the liver consist of the stem cells and their descendants, the hepatoblasts, that give rise to the hepatocytic and biliary lineages. Both hepatic stem cells and most hepatoblasts express EpCAM, but only hepatoblasts are alpha-fetoprotein positive. The percentage of EpCAM positive progenitors in human livers varies with donor age and is about 2.5% in the adult and 12.1% in fetuses. In vivo, hepatic stem cells have been found associated with the canals of Hering. Xeno-transplantation experiments with EpCAM positive human liver cells have revealed their potential for proliferation and differentiation to mature liver parenchymal cells.

實際證據可以看GTEX資料庫中人體正常組織中的EpCAM mRNA表達水平:

腸道的表達是140-250RPKM.

HER2在肺部的表達不到20RKPM, HER2 CART就足以造成肺水腫讓病人5天就死亡。

腸道EpCAM的表達水平是HER2在肺部表達水平的10倍,如果給病人上EpCAM CART, 後果可想而知。

實際情況是四川大學華西醫院等單位正在招募病人進行EpCAM CART臨床試驗, 我覺得以下這幾個搞EpCAM CART臨床試驗的醫生可以去坐牢了, 至少也要取消行醫資格。

除了華西醫院以外,還有安徽省第二人民醫院,安徽省腫瘤醫院和成都醫科大學第一附屬醫院等機構正在招募病人進行EpCAM CART臨床試驗,四家醫院招募的病人總數接近200人。

HER2 CART, EGFR CART, EpCAM CART, 僅僅這三個靶向分子的實體腫瘤CART臨床試驗就有接近400名中國癌症患者面臨高風險的險境, 參與這樣的臨床試驗弊大於利, 在我看來完全沒有必要。

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