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The HLA-A11 or -A33 allele is found in approximately 18% or 10% of the Asian population, respectively, but each of which is a minor allele worldwide, and therefore no clinical trials were previously conducted. To develop a therapeutic peptide vaccine for each of them, we investigated immunological responses of advanced cancer patients with the HLA-A11 + /A11 + (n = 18) or -A33 + /A33 + (n = 13) allele to personalized peptide vaccine (PPV) regimens. The primary sites of HLA-A11+/A11+ or -A33+/A33+ patients were the colon (n = 4 or 2), stomach (2 or 3), breast (3 or 2), lung and pancreas (2 or 2), and so on. For PPV, a maximum of four peptides were selected from nine different peptides capable of binding to HLA-A11 and -A33 molecules based on the pre-existing peptide-specific IgG responses. There were no severe adverse events related to PPV. At the end of the first cycle, peptide-specific CTL responses were augmented in 4/12 or 2/9 of HLA-A11 + /A11 + or -A33 + /A33 + patients, while peptide-specific IgG responses were augmented in 6/14 or 4/10 patients, respectively. Clinical responses consisted of four stable diseases and 14 progressive diseases in HLA-A11 + /A11 + patients, versus seven and six in -A33 + /A33 + patients, respectively. Further clinical study of PPV could be recommended because of the safety and positive immunological responses., (© 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Context: To develop a personalized peptide vaccine (PPV) for recurrent ovarian cancer patients and evaluate its efficacy from the point of view of overall survival (OS), Phase II study of PPV was performed., Patients and Methods: Forty-two patients, 17 with platinum-sensitive and 25 with platinum-resistant recurrent ovarian cancer, were enrolled in this study and received a maximum of four peptides based on HLA-A types and IgG responses to the peptides in pre-vaccination plasma., Results: Expression of 13 of the 15 parental tumor-associated antigens encoding the vaccine peptides, with the two prostate-related antigens being the exceptions, was confirmed in the ovarian cancer tissues. No vaccine-related systemic severe adverse events were observed in any patients. Boosting of cytotoxic T lymphocytes or IgG responses specific for the peptides used for vaccination was observed in 18 or 13 of 42 cases at 6th vaccination, and 19 or 29 of 30 cases at 12th vaccination, respectively. The median survival time (MST) values of the platinum-sensitive- and platinum-resistant recurrent cases were 39.3 and 16.2 months, respectively. The MST of PPV monotherapy or PPV in combination with any chemotherapy during the 1st to 12th vaccination of platinum-sensitive cases was 39.3 or 32.2 months, and that of platinum-resistant cases was 16.8 or 16.1 months, respectively. Importantly, lymphocyte frequency and epitope spreading were significantly prognostic of OS., Discussion and Conclusion: Because of the safety and possible prolongation of OS, a clinical trial of PPV without chemotherapy during the 1st to 12th vaccination in recurrent ovarian cancer patients is merited.

Haptoglobin (Hp) is a well-known acute-phase protein that possibly has influence on tumors through the immune response. This study was conducted to evaluate the correlation between Hp expression and the effect of treatment by cancer peptide vaccines in advanced castration-resistant prostate cancer (CRPC) patients. Hp expression was measured by RT-PCR using peripheral blood mononuclear cells (PBMCs) collected from advanced CRPC patients, who were divided into two groups: long-term survivors and short-term survivors. Before cancer peptide vaccination (pre-vaccination), Hp expression was almost same in the two groups, but after cancer peptide vaccination (post-vaccination), Hp expression was higher in short-term survivors, suggesting that Hp expression in the PBMCs increased in short-term survivors after treatment by cancer peptide vaccines. Our results suggest that Hp expression level in the PBMCs can serve as a prognostic biomarker in treatment by cancer peptide vaccine in advanced CRPC patients.

Objectives. To evaluate the efficacy and safety of personalized peptide vaccination (PPV) combined with chemotherapy for patients with previously treated advanced non-small-cell lung cancer (NSCLC). Patients and Methods. Previously treated PS0-1 patients with IIIB/IV EGFR (epidermal growth factor receptor) wild genotype NSCLC were randomly assigned to docetaxel (60 mg/m(2) on Day 1) plus PPV based on preexisting host immunity or docetaxel plus placebo. Docetaxel administration was repeated every 3 weeks until disease progression. Personalized peptides or placebo was injected subcutaneously weekly in the first 8 weeks and biweekly in subsequent 16 weeks. The primary efficacy endpoint was progression-free survival (PFS). Results. PPV related toxicity was grade 2 or less skin reaction. The median PFS for placebo arm and PPV arm was 52 days and 59 days, respectively. There was no significant difference between two arms by log-rank test (p = 0.42). Interestingly, PFS and overall survival (OS) in humoral immunological responder were significantly longer than those in nonresponder. Conclusion. PPV did not improve the survival in combination with docetaxel for previously treated advanced NSCLC. However, PPV may be efficacious for the humoral immunological responders and a further clinical investigation is needed. [ABSTRACT FROM AUTHOR]

Since both tumor cells and host immune cell repertoires are diverse and heterogeneous, immune responses against tumor-associated antigens should differ substantially among individual cancer patients. Selection of suitable peptide vaccines for individual patients based on the preexisting host immunity before vaccination could induce potent anti-tumor responses that provide clinical benefit to cancer patients. We have developed a novel immunotherapeutic approach of personalized peptide vaccination (PPV) in which a maximum of four human leukocyte antigen (HLA) class IA-matched peptides are selected for vaccination among pooled peptides on the basis of both HLA class IA type and the preexisting host immunity before vaccination. In this review, we discuss our recent results of preclinical and clinical studies of PPV for various types of advanced cancer. [ABSTRACT FROM AUTHOR]

Background: Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC). However, because of delayed immune responses, its clinical benefits, besides for overall survival (OS), are not well captured by the World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Several surrogate markers for evaluation of cancer vaccine, including prostate-specific antigen doubling time (PSADT), are currently sought. The purpose of this study was to assess prospectively the PSA kinetics and immune responses, as well as the efficacy, safety, and biomarkers of personalized peptide vaccination (PPV) in progressive CRPC.Methods: One hundred patients with progressive CRPC were treated with PPV using 2-4 positive peptides from 31 candidate peptides determined by both human leukocyte antigen (HLA) class IA types and the levels of immunoglobulin G (IgG) against each peptide. The association between immune responses and PSADT as well as overall survival (OS) was studied.Results: PPV was safe and well tolerated in all patients with a median survival time of 18.8 months. Peptide-specific IgG and T-cell responses strongly correlated with PSADT (p < 0.0001 and p = 0.0007, respectively), which in turn showed correlation with OS (p = 0.018). Positive IgG responses and prolongation of PSADT during PPV were also significantly associated with OS (p = 0.001 and p = 0.004) by multivariate analysis.Conclusions: PSADT could be an appropriate surrogate marker for evaluation of the clinical benefit of cancer vaccine. Further randomized trials are needed to confirm these results.Trial Registration: UMIN000001850. [ABSTRACT FROM AUTHOR]

We have developed a novel approach in cancer immunotherapy, the personalized peptide vaccination (PPV), in which human leukocyte antigen (HLA)-matched peptides are selected on the basis of preexisting host immunity before vaccination. Recently, we demonstrated the feasibility of PPV in previously treated patients with advanced colorectal cancer, thus warranting further clinical development of this approach. [ABSTRACT FROM AUTHOR]

An abstract of the study "Personalized Peptide Vaccination for Refractory Small Cell Lung Cancer" by Yasuhiro Terazaki and colleagues is presented.