@article{930dc91ec89a465e809d686f03b0bbaa,
title = "Antibody-mediated delivery of viral epitopes to tumors harnesses CMV-specific T cells for cancer therapy",
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.",
author = "Millar, {David G.} and Ramjiawan, {Rakesh R.} and Kosuke Kawaguchi and Nisha Gupta and Jiang Chen and Songfa Zhang and Takashi Nojiri and Ho, {William W.} and Shuichi Aoki and Keehoon Jung and Ivy Chen and Feng Shi and Heather, {James M.} and Kohei Shigeta and Morton, {Laura T.} and Sean Sepulveda and Li Wan and Ricky Joseph and Eleanor Minogue and Ashok Khatri and Aditya Bardia and Ellisen, {Leif W.} and Corcoran, {Ryan B.} and Hata, {Aaron N.} and Pai, {Sara I.} and Jain, {Rakesh K.} and Dai Fukumura and Duda, {Dan G.} and Mark Cobbold",
note = "Funding Information: R.K.J. received an honorarium from Amgen and consultant fees from Ophthotech, SPARC, SynDevRx and XTuit. R.K.J. owns equity in Enlight, SPARC and SynDevRx, and serves on the Board of Directors of XTuit and Boards of Trustees of Tekla Healthcare Investors, Tekla Life Sciences Investors, Tekla Healthcare Opportunities Fund and Tekla World Healthcare Fund. D.G.D. received consultant fees from Bayer and BMS and has research grants from Bayer, Merrimack, Leap, Exelixis and BMS. M.C. and D.G.M. are named inventors on patent application no. WO 2012/123755, which is licensed to Revitope Oncology. D.G.M. and M.C. own equity in Revitope Oncology. M.C. holds equity in Gritstone Oncology. M.C. received consultant fees from Merck Laboratories. M.C. is now an employee of AstraZeneca. Funding Information: D.G.D.{\textquoteright}s work was supported through NIH grant no. R41-CA213678, the Proton Beam/Federal Share Program and MGH ECOR. We thank P. Huang, S. Roberge and T. Hbatmu for the maintenance of gnotobiotic animal colonies and experimental assistance. This work was supported by NCI program project grant nos. P01-CA080124 and R01-CA208205 (to R.K.J. and D.F.), NCI grant nos. R35-CA197743 and U01-CA 224348 (to R.K.J.) and also in part by the Ludwig Center at Harvard. The NIH Tetramer Facility is supported by contract HHSN272201300006C from the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health in the Department of Health and Human Services. Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2020",
month = apr,
day = "1",
doi = "10.1038/s41587-019-0404-8",
language = "English",
volume = "38",
pages = "420--425",
journal = "Nature Biotechnology",
issn = "1087-0156",
publisher = "Nature Publishing Group",
number = "4",
}