Adjuvant cancer peptide vaccine treatment with intravesical BCG therapy for non-muscle-invasive bladder cancer.
e15587 Background: We previously reported safety and high immunogenicity of peptide vaccine treatment using two novel peptides derived from oncoantigens, M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1), for patients with advanced bladder cancer. We further conducted a multi-center phase II clinical trial using the same peptides to investigate the effectiveness to prevent recurrence after TURBt for patients with non-muscle invasive bladder cancer (NMIBC). Methods: The key eligibility criteria were patients with intermediate or high risk for NMIBC, with tumors having expression of MPHOSPH1 and/or DEPDC1, and with HLA class I expression on tumor cells. HLA-A24-restricted MPH and/or DEP derived peptide were subcutaneously administered in combination with intravesical BCG therapy after TUR-Bt. All enrolled patients had received the vaccination without knowing HLA-A status, and the HLA genotypes were used for a key-open marker. The primary endpoint was to examine effect on recurrence free survival (RFS) and secondary endpoint was induction of peptide-specific CTL response, injection site of reaction (ISR) and adverse effect. Results: A total of 133 patients were enrolled. RFS rates at 2 years in all patients were 74.4 %. Although the difference in RFS between the A24(+) and A24(-) groups (77.2% vs. 70.4%) was not statistically significant (p=0.24), that in the ISR-positive group was significantly better than that in the ISR-negative group (81.6% vs. 54.3%, p=0.0004). The peptide vaccine treatment was well-tolerated without any treatment- associated severe adverse events, while the bladder irritability caused by BCG treatment was observed in 64 cases (48.1%). The MPHOSPH1 and DEPDC1 peptide-specific CTL responses in the 24(+) group were observed in 82 % and 83 % of patients, respectively. Four (7.4%) cases in the 24(-) group revealed the peptide-specific CTL response, indicating some cross-reactivity against the vaccinated peptides on other HLA allele(s). Conclusions: Combination immunotherapy of intravesical BCG and cancer peptide vaccine demonstrated the promising clinical effect on recurrence prevention for NMIBC as well as good immunogenicity and safety. Clinical trial information: 00633204.