Rosenberg SA et al. (2006) Altered CD8+ T-cell responses when immunizing with multiepitope peptide vaccines. J Immunother 29: 224–231

Immunization with peptides derived from cancer antigens has been shown to be an effective method of generating antitumor T cells. It has been thought that multiepitope vaccines, consisting of a mixture of peptides, might enhance the response to immunization, as the inflammation caused by more-immunogenic peptides would enhance the response to less-immunogenic components.

In two sequential trials, Rosenberg et al. assessed the response to two cancer-derived peptides, the highly immunogenic gp100:209–217(210M) and the less immunogenic tyrosinase:368–376(370D), in patients at high risk of melanoma recurrence. In the first trial of 31 patients, the vaccines were given separately at two different injection sites. For the second trial of 33 patients, a mixture of the two peptides was administered. When the peptides were injected separately, assays of antipeptide activity revealed a much stronger response to gp100:209–217(210M) than to tyrosinase:368–376(370D). Surprisingly, however, when the mixture of peptides was given, although an enhanced reaction to tyrosinase:368–376(370D) was observed, the response to gp100:209–217(210M) was greatly diminished.

In vitro studies performed by the authors showed that competition between the peptides for binding to MHC molecules might have led to decreased presentation of the gp100:209–217(210M) peptide. Such competition has been previously reported, and could result in the immunodominance of some components of a vaccine mixture over others. The authors caution that interactions between the components of multipeptide vaccines need careful analysis, as the in vivo response to individual components can be altered by local inflammation and by competition between peptides.