Clinical and immunological evaluation of anti-apoptosis protein, survivin-derived peptide vaccine in phase I clinical study for patients with advanced or recurrent breast cancer

Tetsuhiro Tsuruma¹ , Yuji Iwayama¹ , Tosei Ohmura¹ , Tadashi Katsuramaki¹ , Fumitake Hata¹ , Tomohisa Furuhata¹ , Koji Yamaguchi¹ , Yasutoshi Kimura¹ , Toshihiko Torigoe² , Nobuhiko Toyota¹ , Atsuhito Yagihashi³ , Yoshihiko Hirohashi² , Hiroko Asanuma² , Kumiko Shimozawa⁴ , Minoru Okazaki⁵ , Yasuhiro Mizushima⁶ , Naohiro Nomura⁷ , Noriyuki Sato² and Koichi Hirata¹

¹Dept. of Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan

²Dept. of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan

³Dept. of Laboratory Diagnosis, Sapporo Medical University School of Medicine, Sapporo, Japan

⁴Japan Science and Technology Corporation Innovation Plaza Hokkaido, Sapporo, Japan

⁵Dept. of Surgery, Sapporo Nyusen Geka Clinic, Sapporo, Japan

⁶Dept. of Surgery, Ashibetsu Municipal Hospital, Ashibetsu, Japan

⁷Dept. of Medicine, Kitahiroshima Hospital, Kitahiroshima, Japan

author email corresponding author email

Journal of Translational Medicine 2008, 6:24doi:10.1186/1479-5876-6-24


Published:	10 May 2008

Abstract

Background

We previously reported that survivin-2B, a splicing variant of survivin, was expressed in various types of tumors and that survivin-2B peptide might serve as a potent immunogenic cancer vaccine. The objective of this study was to examine the toxicity of and to clinically and immunologically evaluate survivin-2B peptide in a phase I clinical study for patients with advanced or recurrent breast cancer.

Methods

We set up two protocols. In the first protocol, 10 patients were vaccinated with escalating doses (0.1–1.0 mg) of survivin-2B peptide alone 4 times every 2 weeks. In the second protocol, 4 patients were vaccinated with the peptide at a dose of 1.0 mg mixed with IFA 4 times every 2 weeks.

Results

In the first protocol, no adverse events were observed during or after vaccination. In the second protocol, two patients had induration at the injection site. One patient had general malaise (grade 1), and another had general malaise (grade 1) and fever (grade 1). Peptide vaccination was well tolerated in all patients. In the first protocol, tumor marker levels increased in 8 patients, slightly decreased in 1 patient and were within the normal range during this clinical trial in 1 patient. With regard to tumor size, two patients were considered to have stable disease (SD). Immunologically, in 3 of the 10 patients (30%), an increase of the peptide-specific CTL frequency was detected. In the second protocol, an increase of the peptide-specific CTL frequency was detected in all 4 patients (100%), although there were no significant beneficial clinical responses. ELISPOT assay showed peptide-specific IFN-γ responses in 2 patients in whom the peptide-specific CTL frequency in tetramer staining also was increased in both protocols.

Conclusion

This phase I clinical study revealed that survivin-2B peptide vaccination was well tolerated. The vaccination with survivin-2B peptide mixed with IFA increased the frequency of peptide-specific CTL more effectively than vaccination with the peptide alone, although neither vaccination could induce efficient clinical responses. Considering the above, the addition of another effectual adjuvant such as a cytokine, heat shock protein, etc. to the vaccination with survivin-2B peptide mixed with IFA might induce improved immunological and clinical responses.