Author: ["David G. Millar","Rakesh R. Ramjiawan","Kosuke Kawaguchi","Nisha Gupta","Jiang Chen","Songfa Zhang","Takashi Nojiri","William W. Ho","Shuichi Aoki","Keehoon Jung","Ivy Chen","Feng Shi","James M. Heather","Kohei Shigeta","Laura T. Morton","Sean Sepulveda
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Abstract
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 linkers. These APECs redirect pre-existing CMV immunity against tumor cells in vitro and in mouse cancer models. In vitro, APECs activated specifically CMV-reactive effector T cells whereas a bispecific T-cell engager activated both effector and regulatory T cells. Our approach may provide an effective alternative in cancers that are not amenable to checkpoint inhibitors or other immunotherapies. Anti-tumor activity of cytomegalovirus (CMV)-specific CD8 T cells is achieved by antibody-mediated delivery of CMV epitopes.Cite this article
Millar, D.G., Ramjiawan, R.R., Kawaguchi, K. et al. Antibody-mediated delivery of viral epitopes to tumors harnesses CMV-specific T cells for cancer therapy. Nat Biotechnol 38, 420–425 (2020). https://doi.org/10.1038/s41587-019-0404-8 