Much of the recent work on the development of active, specific immunotherapy of cancer has focused on the induction of CD8+ cytotoxic T-lymphocyte (CTL) responses, and several studies have shown that it is possible to stimulate tumour-specific CTLs using dendritic cells (DCs) that are loaded with tumour antigens. But CD4+ T-helper type 1 (TH1) cells are also important components of effective immune responses. In this study, Schuler–Thurner and colleagues provide the first evidence that DCs that are loaded with tumour-specific peptides can rapidly induce TH1 responses in cancer patients that are readily detectable ex vivo.

The DCs that were used for vaccination in this study were derived from blood monocytes that were matured ex vivo using a defined cocktail (consisting of interleukin (IL)-1β, IL-6, tumour-necrosis factor and prostaglandin E2) and cryopreserved before use. Aliquots of cells were thawed on the day of vaccination and loaded with various MHC class-I- and -II-restricted peptides. Patients with incurable melanoma were treated with five biweekly vaccinations of DCs, followed by assessment one month after the final vaccination.

The results showed that the vaccination protocol induced a rapid TH1 response in patients, both to a control immunizing antigen and also to defined MHC class-II-restricted tumour antigens. Immune responses were assessed on the basis of interferon-γ production using ELISPOT assays and antigen-specific proliferative responses.

So, the results from this Phase I trial provide convincing evidence that cryopreserved DCs can induce TH1 responses against tumour antigens without significant toxicity, and it also encourages further development of DC-based vaccination technology.