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Immunological mechanisms of oncolytic adenoviral therapy
Date:1/26/2012

the therapeutic effects on cancer. Some studies have shown that suppressing the immune system could enhance the efficacy of oncolytic vectors. On the other hand, recent preclinical and clinical studies have suggested that the immune response plays an important role in mediating the antitumor efficacy. Therefore, the influence of immune responses on oncolytic therapy is complex. Because of the species specificity of adenoviral replication, it was widely assumed that adenoviral replication would not occur in mouse tumors. Consequently, oncolytic adenoviral vectors have been commonly evaluated in immunodeficient mouse-human tumor xenograft models, which do not accurately reflect what happens in humans treated with oncolytic adenovirus. A team led by Professor Yaohe Wang from the Center for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, previously screened a panel of mouse tumor cell lines and identified two cell linesCMT 93 (a murine rectal cancer cell line) and CMT64 (a murine non-small-cell lung cancer cell line) with significant permissibility for adenoviral gene expression, cytopathic effects, and/or replication.

In this work, the team lead by Professor Wang Shengdian evaluated the roles of immune components in oncolytic adenoviral therapy with a murine tumor by subcutaneously inoculating CMT 93 cells into syngeneic C57BL/6 mice. They found that CD8+ T cells, but not CD4+ T cells or natural killer cells, are critical mediators of the antitumor efficacy of oncolytic adenovirus by deletion of the corresponding cell subsets with specific antibodies. Intratumoral injection of adenovirus serotype 5 (Ad5) could induce intensive infiltration of CD8+ T cells into the tumor, and increase tumor-specific interferon-γ production and cytotoxic T lymphocyte activity. The anti-tumor T cell responses induced by Ad5 therapy produced long-term tumor-specific memory immune responses that protected the cured mice well from tumor rechallenge
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Contact: Wang Shengdian
sdwang@moon.ibp.ac.cn
0086-106-488-8493
Science in China Press
Source:Eurekalert

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