Phase I clinical trial of multi-antigen peptide vaccines therapy using cancer-testis antigens for patients with advanced or recurrent breast cancer.

Abstract

e13037 Background: Cancer-testis (CT) antigens are proteins that are normally expressed only in the human germline, but are also present in a significant subset of malignant tumors. The practical importance of these proteins is that, due to their restricted expression pattern, they are frequently recognized by the immune system of cancer patients. Moreover, this antigenicity has raised the possibility of their use as vaccines to stimulate immune responses in order to combat tumor growth. As a result, many aspects of CT antigens have been examined in studies performed worldwide. Here we report the results of a phase I clinical trial combining five kinds of CT peptide (CDCA1,URLC10,KIF20A,DEPDC1,MPHOSPH1) vaccination. Methods: The subjects of the trial were HLA-A24-positive patients with metastatic and advanced breast cancer. The mixture of peptides was subcutaneously injected weekly with dose-escalation (doses of 0.5, 1, and 2 mg of each peptide/body, three patients/cohort). Safety, efficacy and immunological parameters were assessed. Results: No adverse events were observed in any patients. Of the 9 patients who completed at least one cycle of the treatment, 4 (44%) developed immunological reactions at the injection site. Specific cytotoxic T lymphocytes (CTLs) reacting to any peptide were induced in 7 (78%) of the 9 patients. Of the 7 patients who completed at least two cycles of the treatment, tumor regression compatible with stable disease (SD) was noted in 4 patients. The remaining patients had progressive disease (PD). The vaccine therapy was tolerable and safe at all doses. Conclusions: Combination therapy with CT antigens has therapeutic potential for patients with breast cancer. Peptide-specific CTLs against peptides in the vaccine were induced at a high rate, even in heavily pretreated patients. From an immunological perspective, the optimal dose for further clinical trials is ≥1 mg/body.