嵌合抗原受体
抗原
医学
癌症研究
人口
癌症干细胞
转移
免疫疗法
免疫学
肿瘤科
癌症
内科学
免疫系统
环境卫生
作者
Agata Kieliszek,Daniel Mobilio,Deepak Upreti,Darin Bloemberg,Laura Escudero,Jacek M. Kwiecień,Zahra Alizada,Kui Zhai,P T Ang,Shawn C. Chafe,Parvez Vora,Chitra Venugopal,Sheila K. Singh
标识
DOI:10.1158/1078-0432.ccr-23-1735
摘要
Abstract Purpose: Brain metastases (BM) are mainly treated palliatively with an expected survival of less than 12 months after diagnosis. In many solid tumors, the human neural stem cell marker glycoprotein CD133 is a marker of a tumor-initiating cell population that contributes to therapy resistance, relapse, and metastasis. Experimental Design: Here, we use a variant of our previously described CD133 binder to generate second-generation CD133-specific chimeric antigen receptor T cells (CAR-T) to demonstrate its specificity and efficacy against multiple patient-derived BM cell lines with variable CD133 antigen expression. Results: Using both lung- and colon-BM patient-derived xenograft models, we show that a CD133-targeting CAR-T cell therapy can evoke significant tumor reduction and survival advantage after a single dose, with complete remission observed in the colon-BM model. Conclusions: In summary, these data suggest that CD133 plays a critical role in fueling the growth of BM, and immunotherapeutic targeting of this cell population is a feasible strategy to control the outgrowth of BM tumors that are otherwise limited to palliative care. See related commentary by Sloan et al., p. 477
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