Immunotherapy with cancer peptides in combination with intravesical bacillus Calmette-Guerin for patients with non-muscle invasive bladder cancer

A phase I study using two peptide vaccines derived from M phase phosphoprotein 1 (MPHOSPH1) and DEP domain containing 1 (DEPDC1) demonstrated promising results for the treatment of advanced bladder cancer. Therefore, we further tested the ability of these peptides to prevent recurrence after transurethral resection of the bladder tumor in patients with non-muscle invasive bladder cancer (NMIBC).

127 patients were enrolled in a multicenter, non-randomized phase II clinical trial. The primary endpoint was recurrence-free survival (RFS) rate, and secondary endpoints were safety and immunological response. HLA-A24-restricted peptides were subcutaneously administered in addition to intravesical BCG therapy. The exploratory endpoint evaluated differences of RFS rate between HLA-A*2402-positive (A24(+)) and -negative (A24(-)) groups.

A 2-year RFS rate in all patients was 74.0%. The RFS rate in the A24(+) group (n = 75) and in the A24(-) group (n = 52) were 76.0 and 71.2%, respectively. This vaccine therapy was well-tolerated and feasible. MPHOSPH1 and DEPDC1 peptide-specific cytotoxic T lymphocyte responses were observed in 75.8 and 77.5% of the A24(+) group, respectively. Patients having both peptide-specific CTL responses showed significantly better RFS than patients without CTL response (P = 0.014). In the A24(+) group, patients who had positive reaction at the injection sites (RAI) had significantly lower rates of recurrence than RAI-negative patients (P = 0.0019).

Cancer peptide vaccines in combination with intravesical BCG therapy demonstrated good immunogenicity and safety, and may provide benefit for preventing recurrence of NMIBC.

Cancer immunology, immunotherapy : CII. 2018 Jul 03 [Epub ahead of print]

Wataru Obara, Isao Hara, Yoichiro Kato, Renpei Kato, Keiji Inoue, Fuminori Sato, Hiromitsu Mimata, Yusuke Nakamura, Tomoaki Fujioka

Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan. ., Department of Urology, Wakayama Medical University, Wakayama, Japan., Department of Urology, Iwate Medical University School of Medicine, 19-1 Uchimaru, Morioka, 020-8505, Japan., Department of Urology, Kochi Medical School, Nankoku, Japan., Department of Urology, Faculty of Medicine, Oita University, Yufu, Japan., Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL, USA.


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