OBJECTIVE: Oncolytic forms of attenuated Vaccinia virus are now in clinical development, assessing the compatibility of this novel treatment with radiotherapy may reveal exploitable synergistic relationships. MATERIALS AND METHODS: In vitro analyses of cell killing, cell cycle effects and caspase activation were carried out on HN3, HN5, CAL27, Detroit, SIHN5B, and PJ41 cells. In vivo studies of the virus and X-radiation were performed on H&N xenografts in CD1 nude mice. RESULTS: Cell killing in vitro was demonstrated to be dose- and time-dependent. Infection causes an increase in S-phase and sub-G1 cells. A dose dependent increase in active caspase-3 indicated induction of apoptosis. Xenografts injected with Vaccinia stabilised and frequently completely regressed. Combination with radiation generated additional cell death, induction of caspase activity and in vivo further improved long term regression rates. CONCLUSIONS: These data support continued exploration of this therapy combination and indicates potential for clinical trials in head and neck cancer.
OBJECTIVE: Oncolytic forms of attenuated Vaccinia virus are now in clinical development, assessing the compatibility of this novel treatment with radiotherapy may reveal exploitable synergistic relationships. MATERIALS AND METHODS: In vitro analyses of cell killing, cell cycle effects and caspase activation were carried out on HN3, HN5, CAL27, Detroit, SIHN5B, and PJ41 cells. In vivo studies of the virus and X-radiation were performed on H&N xenografts in CD1nude mice. RESULTS: Cell killing in vitro was demonstrated to be dose- and time-dependent. Infection causes an increase in S-phase and sub-G1 cells. A dose dependent increase in active caspase-3 indicated induction of apoptosis. Xenografts injected with Vaccinia stabilised and frequently completely regressed. Combination with radiation generated additional cell death, induction of caspase activity and in vivo further improved long term regression rates. CONCLUSIONS: These data support continued exploration of this therapy combination and indicates potential for clinical trials in head and neck cancer.
Authors: Kathryn Ottolino-Perry; Sergio A Acuna; Fernando A Angarita; Clara Sellers; Siham Zerhouni; Nan Tang; J Andrea McCart Journal: Mol Oncol Date: 2015-05-06 Impact factor: 6.603
Authors: Michelle J Wilkinson; Henry G Smith; Gráinne McEntee; Joan Kyula-Currie; Tim D Pencavel; David C Mansfield; Aadil A Khan; Victoria Roulstone; Andrew J Hayes; Kevin J Harrington Journal: Oncotarget Date: 2016-12-06
Authors: D C Mansfield; J N Kyula; N Rosenfelder; J Chao-Chu; G Kramer-Marek; A A Khan; V Roulstone; M McLaughlin; A A Melcher; R G Vile; H S Pandha; V Khoo; K J Harrington Journal: Gene Ther Date: 2016-01-27 Impact factor: 5.250
Authors: Michelle J Wilkinson; Henry G Smith; Timothy D Pencavel; David C Mansfield; Joan Kyula-Currie; Aadil A Khan; Gráinne McEntee; Victoria Roulstone; Andrew J Hayes; Kevin J Harrington Journal: Int J Cancer Date: 2016-05-24 Impact factor: 7.396