| Literature DB >> 30753824 |
Hongwei Du1, Koichi Hirabayashi1, Sarah Ahn2, Nancy Porterfield Kren3, Stephanie Ann Montgomery4, Xinhui Wang5, Karthik Tiruthani6, Bhalchandra Mirlekar3, Daniel Michaud7, Kevin Greene8, Silvia Gabriela Herrera1, Yang Xu1, Chuang Sun1, Yuhui Chen1, Xingcong Ma1, Cristina Rosa Ferrone5, Yuliya Pylayeva-Gupta3, Jen Jen Yeh9, Rihe Liu10, Barbara Savoldo11, Soldano Ferrone5, Gianpietro Dotti12.
Abstract
The high expression across multiple tumor types and restricted expression in normal tissues make B7-H3 an attractive target for immunotherapy. We generated chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR-Ts) and found that B7-H3.CAR-Ts controlled the growth of pancreatic ductal adenocarcinoma, ovarian cancer and neuroblastoma in vitro and in orthotopic and metastatic xenograft mouse models, which included patient-derived xenograft. We also found that 4-1BB co-stimulation promotes lower PD-1 expression in B7-H3.CAR-Ts, and superior antitumor activity when targeting tumor cells that constitutively expressed PD-L1. We took advantage of the cross-reactivity of the B7-H3.CAR with murine B7-H3, and found that B7-H3.CAR-Ts significantly controlled tumor growth in a syngeneic tumor model without evident toxicity. These findings support the clinical development of B7-H3.CAR-Ts.Entities:
Keywords: 4-1BB; B7-H3; CD28; PD-1/PD-L1; chimerc antigen receptor; neuroblastoma; ovarian cancer; pancreatic cancer; solid tumors
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Year: 2019 PMID： 30753824 PMCID： PMC6645919 DOI： 10.1016/j.ccell.2019.01.002
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743