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

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 multip...

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Bibliographic Details
Published in:	Cancer science Vol. 109; no. 9; pp. 2660 - 2669
Main Authors:	Noguchi, Masanori, Koga, Noriko, Moriya, Fukuko, Suekane, Shigetaka, Yutani, Shigeru, Yamada, Akira, Shichijo, Shigeki, Kakuma, Tatuyuki, Itoh, Kyogo
Format:	Journal Article
Language:	English
Published:	England John Wiley & Sons, Inc 01-09-2018 John Wiley and Sons Inc
Subjects:	Acid phosphatase Adult Aged Aged, 80 and over Antigen (tumor-associated) Antigens Antigens, Neoplasm - analysis Cancer vaccines Cancer Vaccines - immunology Candidates Castration Clinical trials Female Histocompatibility antigen HLA Humans Immune response Immunotherapy Lck protein Lymph nodes Male Metastases Middle Aged Original Parathyroid hormone-related protein Patients Peptides peptide‐based cancer vaccine Prostate cancer Regression analysis Studies Survival analysis Tumor cells Urologic Neoplasms - immunology Urologic Neoplasms - mortality Urologic Neoplasms - therapy Urothelial cancer Vaccination Vaccines, Subunit - immunology United States > US Japan peptide-based cancer vaccine prostate cancer urothelial cancer survival analysis immunotherapy
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Summary:	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. Using contributing peptides selected by both survival data and pre‐existing immunity in personalized peptide vaccine treatment may enhance the clinical benefits for urological cancer patients.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Clinical Trials Registry: UMIN000001850, UMIN000005329, UMIN000010290, UMIN000001854 and UMIN000003157.
ISSN:	1347-9032 1349-7006
DOI:	10.1111/cas.13709