Turning foe into friend with lentiviral vectors

Currently, there is no vaccine available that is able to cure cancer. The success of an antitumor vaccine will depend on its ability to induce robust and sustained tumor-specific immune responses. There is evidence to suggest that antitumor vaccination can induce such responses and even tumor regression. However, to date these regressions have not been long-lasting. Researchers at the Ludwig Institute for Cancer Research in Switzerland have developed a lentiviral vaccine which following injection into mice is capable of inducing an antigen-specific T cell response. This approach represents an attractive candidate for cancer therapy.

The crucial stimulation of a T cell response is dependent on the presentation of the antigen by host dendritic cells (DCs). As part of earlier strategies, the antigen of interest has been transferred to host DCs (by a process called “transduction”) outside the body and the DCs then reintroduced into the host. Unfortunately, this is a costly and labor-intensive process.

In the June 2 issue of the Journal of Clinical Investigation, Christopher Esslinger and colleagues describe their use of a third generation lentivector capable of transducing DCs in vivo in mice and inducing a very strong antigen-specific immune response. The immune response was shown to be superior to methods using DCs transduced outside the body in terms of both amplitude and persistence.

“Our results demonstrate that the time-consuming and costly steps currently used to elicit tumor-specific cytotoxic T lymphocyte responses through the transfer of ex-vivo manipulated DCs could be replaced by the much simpler direct in vivo administration of antigen recombinant lentivectors” states Dr. Esslinger.

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TITLE: In vivo administration of a lentiviral vaccine targets DCs and induces efficient CD8+ T cell responses