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E D I T O R I A L
An empiric victory
Provenge already looks like the product of a bygone era.
2010 Nature America, Inc. All rights reserved.
The approval of Provenge is remarkable. It represents a triumph of esotericism over the scientific method; a victory for doggedness over
diligence; a success for clinical and manufacturing brawn over molecular precision. As the first approved cellular vaccine against cancer, it vindicates the persistence of those who have labored for decades to obtain clinical validation of the approach. More specifically, the product proves that the T-cell arm of the adaptive response can be harnessed to fight advanced cancers. These are good things. But there are also reasons why Provenge is likely to achieve only limited commercial success.
The Provenge story starts with studies at the Stanford University School of Medicine published in 1997 (J. Immunol. 159, 31133117) that showed that a cytotoxic T-lymphocyte (CTL) response to prostatic acid phosphatase (PAP) antigen could result in the destruction of PAP-bearing tissues. In other words, eliciting T-cell immunity, and not solely an antibody response, might be effective as a cancer immunotherapy. But as tumors are so adept at cloaking themselves from immune surveillance, the question was how to elicit an appropriate cellular response to the tumor antigen of interest.
Dendreons solution was to induce cellular immunity ex vivo by removing and semipurifying (by centrifugation) patients antigen-presenting cells (APCs), or dendritic cells, and exposing them to tumor antigen super-charged with an immunomodulator. The specific trick,...