CD8(+) T-cell Immune Evasion Enables Oncolytic Virus Immunotherapy.
EBioMedicine
; 5: 59-67, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-27077112
ABSTRACT
Although counteracting innate defenses allows oncolytic viruses (OVs) to better replicate and spread within tumors, CD8(+) T-cells restrict their capacity to trigger systemic anti-tumor immune responses. Herpes simplex virus-1 (HSV-1) evades CD8(+) T-cells by producing ICP47, which limits immune recognition of infected cells by inhibiting the transporter associated with antigen processing (TAP). Surprisingly, removing ICP47 was assumed to benefit OV immuno-therapy, but the impact of inhibiting TAP remains unknown because human HSV-1 ICP47 is not effective in rodents. Here, we engineer an HSV-1 OV to produce bovine herpesvirus UL49.5, which unlike ICP47, antagonizes rodent and human TAP. Significantly, UL49.5-expressing OVs showed superior efficacy treating bladder and breast cancer in murine models that was dependent upon CD8(+) T-cells. Besides injected subcutaneous tumors, UL49.5-OV reduced untreated, contralateral tumor size and metastases. These findings establish TAP inhibitor-armed OVs that evade CD8(+) T-cells as an immunotherapy strategy to elicit potent local and systemic anti-tumor responses.
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MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
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Neoplasias da Mama
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Proteínas do Envelope Viral
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Vírus Oncolíticos
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Terapia Viral Oncolítica
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article