Survival analysis of multiple peptide vaccination for the selection of correlated peptides in urological cancers.

Abstract

Peptide-based cancer vaccines are able to induce strong immune responses, but their clinical results are unsatisfactory. To determine clinically correlated peptides, we analyzed survival data from urological cancer patients treated by personalized peptide vaccination (PPV), in which different multiple peptides were used for individual patients based on human leukocyte antigen (HLA) type and pre-existing immunity. Survival data were obtained from a database of 265 urological cancer patients treated in 5 clinical PPV trials comprising 154 patients with castration-resistant prostate cancer (CRPC) and 111 patients with advanced urothelial cancer (UC). Expression of tumor-associated antigens (TAA) was evaluated in 10 prostate cancer tissues, 4 metastatic lymph nodes from prostate cancer, and 10 UC tissues using immunohistochemical staining. Clinical efficacy of individual peptides for overall survival was evaluated by the Cox proportional hazards regression model. All TAA coding candidate peptides used in PPV treatment were expressed in tumor cells from prostate cancer and UC samples except for p56Lck in both, and prostate-specific antigen (PSA), prostatic acid phosphatase (PAP) and prostate-specific membrane antigen (PSMA) in the UC samples. Patients with the following peptides had a significantly longer survival than patients without the peptides (hazard ratio <1.0, 95% confidence intervals <1.0 and P < .05): SART3-109, PTHrP-102, HNPRL-140, SART3-302 and Lck-90 in CRPC patients, and EGF-R-800, Lck-486, PSMA-624, CypB-129 and SART3-734 in advanced UC patients, respectively. Correlated peptides selected using both survival data and pre-existing immunity for PPV treatment may enhance the clinical benefits for urological cancer patients.

• Authors: Masanori Noguchi, Noriko Koga, Fukuko Moriya, Shigetaka Suekane, Shigeru Yutani, Akira Yamada, Shigeki Shichijo, Tatuyuki Kakuma, Kyogo Itoh
• Journal: Cancer science (Cancer Sci) Vol. 109 Issue 9 Pg. 2660-2669 (Sep 2018) ISSN: 1349-7006 [Electronic] England
• PMID: 29938870 (Publication Type: Journal Article)
• Copyright: © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• Antigens, Neoplasm
• Cancer Vaccines
• Vaccines, Subunit

Topics

• Adult
• Aged
• Aged, 80 and over
• Antigens, Neoplasm (analysis)
• Cancer Vaccines (immunology)
• Female
• Humans
• Male
• Middle Aged
• Urologic Neoplasms (immunology, mortality, therapy)
• Vaccination
• Vaccines, Subunit (immunology)