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Antibody-mediated delivery of viral epitopes to tumors harnesses CMV-specific T cells for cancer therapy

Nat Biotechnol. 2020; 
Millar DG, Ramjiawan RR, Kawaguchi K, Gupta N, Chen J, Zhang S, Nojiri T, Ho WW, Aoki S, Jung K, Chen I, Shi F, Heather JM, Shigeta K, Morton LT, Sepulveda S, Wan L, Joseph R, Minogue E, Khatri A, Bardia A, Ellisen LW, Corcoran RB, Hata AN, Pai SI, Jain RK, Fukumura D, Duda DG, Cobbold M
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摘要

Several cancer immunotherapy approaches, such as immune checkpoint blockade and adoptive T-cell therapy, boost T-cell activity against the tumor, but these strategies are not effective in the absence of T cells specific for displayed tumor antigens. Here we outline an immunotherapy in which endogenous T cells specific for a noncancer antigen are retargeted to attack tumors. The approach relies on the use of antibody-peptide epitope conjugates (APECs) to deliver suitable antigens to the tumor surface for presention by HLA-I. To retarget cytomegalovirus (CMV)-specific CD8+ T cells against tumors, we used APECs containing CMV-derived epitopes conjugated to tumor-targeting antibodies via metalloprotease-sensitive l... More

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