作者
Karin Straathof, Barry Flutter, Rebecca Wallace, Neha Jain, Thalia Loka, Sarita Depani, Gary Wright, Simon Thomas, Gordon Weng-Kit Cheung, Talia Gileadi, Sian Stafford, Evangelia Kokalaki, Jack Barton, Clare Marriott, Dyanne Rampling, Olumide Ogunbiyi, Ayse U Akarca, Teresa Marafioti, Sarah Inglott, Kimberly Gilmour, Muhammad Al-Hajj, William Day, Kieran McHugh, Lorenzo Biassoni, Natalie Sizer, Claire Barton, David Edwards, Ilaria Dragoni, Julie Silvester, Karen Dyer, Stephanie Traub, Lily Elson, Sue Brook, Nigel Westwood, Lesley Robson, Ami Bedi, Karen Howe, Ailish Barry, Catriona Duncan, Giuseppe Barone, Martin Pule, John Anderson
发表日期
2020/11/25
期刊
Science Translational Medicine
卷号
12
期号
571
页码范围
eabd6169
出版商
American Association for the Advancement of Science
简介
The reprogramming of a patient’s immune system through genetic modification of the T cell compartment with chimeric antigen receptors (CARs) has led to durable remissions in chemotherapy-refractory B cell cancers. Targeting of solid cancers by CAR-T cells is dependent on their infiltration and expansion within the tumor microenvironment, and thus far, fewer clinical responses have been reported. Here, we report a phase 1 study (NCT02761915) in which we treated 12 children with relapsed/refractory neuroblastoma with escalating doses of second-generation GD2-directed CAR-T cells and increasing intensity of preparative lymphodepletion. Overall, no patients had objective clinical response at the evaluation point +28 days after CAR-T cell infusion using standard radiological response criteria. However, of the six patients receiving ≥108/meter2 CAR-T cells after fludarabine/cyclophosphamide conditioning …
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