ince the turn of the century, immunologists have been fascinated by the possible application of immunology to the treatment of cancer. However, it was only after the identification of the first human tumorassociated antigen (TAA) 1 , less than a decade ago, that development of specific vaccination procedures for cancer patients became possible. Since then, different epitopes recognized by CD8 Ο© cytotoxic T lymphocytes (CTLs) from neoplastic patients have been identified (reviewed in Refs 2, 3). Antigen-specific vaccines are being designed and, although vaccinations with full-length recombinant proteins or vectors are also being tested clinically, the only data that have been published so far have emerged from Phase I/II clinical trials using tumor synthetic peptides presented by common human major histocompatibility complex (MHC) class I (HLA) alleles.
These vaccination procedures should focus the immune response on the immunogenic epitopes, providing specificity to the antitumor immune response. The unlimited amount of synthetic antigen should also enable therapeutic schedules requiring several boosts, as well as the treatment of patients even when only a small amount of the autologous tumor (needed to verify the antigen expression) is available. Moreover, the purity of the antigen, which should facilitate an effective recruitment of tumor-specific CTLs, together with the applicability to neoplasms that contain shared epitopes among tumors of different histotype, make the use of synthetic peptides for cancer immunotherapy very appealing.
Phase I clinical trials have been carried out using synthetic peptides corresponding to defined TAAs, in the absence or in the presence of adjuvants, or pulsed on autologous monocytes or dendritic cells (DCs) (see Table 1). These studies indicate that vaccination with synthetic peptides is well tolerated, with occasional occurrence of mild fever and inflammation at the site of injection. Nonetheless, it should be pointed out that there is usually a poor correlation between induction of specific