Open AccessOncolytic adenovirus expressing bispecific antibody targets T‐cell cytotoxicity in cancer biopsies
Author(s) -
Freedman Joshua D,
Hagel Joachim,
Scott Eleanor M,
Psallidas Ioannis,
Gupta Avinash,
Spiers Laura,
Miller Paul,
Kanellakis Nikolaos,
Ashfield Rebecca,
Fisher Kerry D,
Duffy Margaret R,
Seymour Leonard W
Publication year - 2017
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201707567
Subject(s) - oncolytic virus , oncolytic adenovirus , lytic cycle , cancer research , cytotoxic t cell , biology , cytotoxicity , cancer cell , antibody , t cell , virotherapy , microbiology and biotechnology , cancer , virus , virology , immune system , immunology , in vitro , biochemistry , genetics
Oncolytic viruses exploit the cancer cell phenotype to complete their lytic life cycle, releasing progeny virus to infect nearby cells and repeat the process. We modified the oncolytic group B adenovirus EnAdenotucirev (EnAd) to express a bispecific single‐chain antibody, secreted from infected tumour cells into the microenvironment. This bispecific T‐cell engager (Bi TE ) binds to Ep CAM on target cells and cross‐links them to CD 3 on T cells, leading to clustering and activation of both CD 4 and CD 8 T cells. Bi TE transcription can be controlled by the virus major late promoter, limiting expression to cancer cells that are permissive for virus replication. This approach can potentiate the cytotoxicity of EnAd, and we demonstrate using primary pleural effusions and peritoneal malignant ascites that infection of cancer cells with the Bi TE ‐expressing EnAd leads to activation of endogenous T cells to kill endogenous tumour cells despite the immunosuppressive environment. In this way, we have armed EnAd to combine both direct oncolysis and T cell‐mediated killing, yielding a potent therapeutic that should be readily transferred into the clinic.