• Antigen
• CD58
• Glioma
• Immune
• Mechanism
• Prognosis

• cancer-testis antigens
• immune phenotype
• immune-oncology
• non-small cell lung cancer

• 21 1790 Cancerfonden
• 2015.0344 Knut och Alice Wallenbergs Stiftelse
• Lions Clubs International Foundation
• Sjöbergstiftelsen
• 2021-02693 Vetenskapsrådet

• biomarkers
• castration-resistant prostate cancer
• dendritic cell-based vaccines
• immunotherapy
• prostate cancer
• tumor microenvironment

• Cancer immunotherapy
• Nanoparticle
• Nanovaccine
• PD-L1 gene silence
• Protamine

• Humans
• B7-H1 Antigen/genetics
• B7-H1 Antigen/metabolism
• Prospective Studies
• Neoplasms/drug therapy
• Nanoparticles
• Immunotherapy/methods

• CD8+ T cell immunity
• HER-2(780–788)
• HER-2/neu
• IL-8
• TGF-β
• prostate cancer
• survival

In recent history, immunotherapy has become a viable cancer therapeutic option. However, over many years, its tenets have changed, and it now comprises a range of cancer-focused immunotherapies. Clinical trials are currently looking into monotherapies or combinations of medicines that include immune checkpoint inhibitors (ICI), CART cells, DNA vaccines targeting viruses, and adoptive cellular therapy. According to ongoing studies, the discipline should progress by incorporating patient-tailored immunotherapy, immune checkpoint blockers, other immunotherapeutic medications, hormone therapy, radiotherapy, and chemotherapy. Despite significantly increasing morbidity, immunotherapy can intensify the therapeutic effect and enhance immune responses. The findings for the immunotherapy treatment of advanced prostate cancer (PCa) are compiled in this study, showing that is possible to investigate the current state of immunotherapy, covering new findings, PCa treatment techniques, and research perspectives in the field’s unceasing evolution.

• biomarkers
• combination immunotherapy
• immune checkpoints
• immunotherapy
• prostate cancer

Peptide-based cancer vaccines have been shown to boost immune systems to kill tumor cells in cancer patients. However, designing an effective T cell epitope peptide-based cancer vaccine still remains a challenge and is a major hurdle for the application of cancer vaccines. In this study, we constructed for the first time a library of peptide-based cancer vaccines and their clinical attributes, named CancerVaccine (https://peptidecancervaccine.weebly.com/). To investigate the association factors that influence the effectiveness of cancer vaccines, these peptide-based cancer vaccines were classified into high (HCR) and low (LCR) clinical responses based on their clinical efficacy. Our study highlights that modified peptides derived from artificially modified proteins are suitable as cancer vaccines, especially for melanoma. It may be possible to advance cancer vaccines by screening for HLA class II affinity peptides may be an effective therapeutic strategy. In addition, the treatment regimen has the potential to influence the clinical response of a cancer vaccine, and Montanide ISA-51 might be an effective adjuvant. Finally, we constructed a high sensitivity and specificity machine learning model to assist in designing peptide-based cancer vaccines capable of providing high clinical responses. Together, our findings illustrate that a high clinical response following peptide-based cancer vaccination is correlated with the right type of peptide, the appropriate adjuvant, and a matched HLA allele, as well as an appropriate treatment regimen. This study would allow for enhanced development of cancer vaccines.

• Adjuvants, Immunologic
• Cancer Vaccines
• Humans
• Melanoma
• Mineral Oil
• Peptides
• Vaccines, Subunit

• Cancer Prevention and Research Institute of Texas

• breast cancer
• colon cancer
• immune kinetics
• lung adenocarcinoma
• personized peptide vaccine
• recurrence prevention

• Active cancer immunotherapy
• Antibodies
• Cancer vaccines
• Immune checkpoint inhibition
• Passive cancer immunotherapy
• T cell therapies

• T lymphocytes
• hepatocellular carcinoma
• immunotherapy
• mutation screening

• CXCR-4
• Cancer
• PD-L1
• desmoplasia
• immunoresistance
• immunotherapy

To develop a neoantigen-targeted personalized cancer treatment for non-small cell lung cancer (NSCLC), neoantigens were obtained from collected human lung cancer samples, and the utility of neoantigen and neoantigen-reactive T cells (NRTs) was assessed.

Tumor specimens from three patients with NSCLC were obtained and analyzed by whole-exome sequencing, and neoantigens were predicted accordingly. Dendritic cells and T lymphocytes were isolated, NRTs were elicited and IFN-γ ELISPOT tests were conducted. HLA-A2.1/K^b transgenic mice were immunized with peptides from HLA-A*02:01⁺patient with high immunogenicity, and NRTs were subjected to IFN-γ, IL-2 and TNF-α ELISPOT as well as time-resolved fluorescence assay for cytotoxicity assays to verify the immunogenicity in vitro. The HLA-A*02:01⁺lung cancer cell line was transfected with minigene and inoculated into the flanks of C57BL/6^nu/nu mice and the NRTs induced by the immunogenic polypeptides from autologous HLA-A2.1/K^b transgenic mice were adoptively transfused to verify their immunogenicity in vivo.

Multiple putative mutation-associated neoantigens with strong affinity for HLA were selected from each patient. Immunogenic neoantigen were identified in all three NSCLC patients, the potency of ACAD8-T105I, BCAR1-G23V and PLCG1-M425L as effective neoantigen to active T cells in suppressing tumor growth was further proven both in vitro and in vivo using HLA-A2.1/Kb transgenic mice and tumor-bearing mouse models.

Neoantigens with strong immunogenicity can be screened from NSCLC patients through the whole-exome sequencing of patient specimens and machine-learning-based neoantigen predictions. NRTs shown efficient antitumor responses in transgenic mice and tumor-bearing mouse models. Our results indicate that the development of neoantigen-based personalized immunotherapies in NSCLC is possible.

Neoantigens with strong immunogenicity were screened from NSCLC patients. This research provides evidence suggesting that neoantigen-based therapy might serve as feasible treatment for NSCLC.

• immunotherapy
• neoantigen
• neoantigen-reactive T cells (NRTs)
• non-small cell lung cancer (NSCLC)
• tumor vaccine

• CTL responses
• DC
• Nasal administration
• PSMA
• Subunit vaccine
• mGM-CSF

• SNP genotyping
• cancer immunotherapy
• fluorescent quenching probe
• loop-mediated isothermal amplification
• personalized peptide vaccines

• cancer vaccines
• combination immunotherapy
• immunotherapy
• metastatic castrate-resistant prostate cancer

The aim of the present study was to determine the factors associated with reduced clinical benefits of personalized peptide vaccination (PPV) for pancreatic cancer. Phase II PPV clinical trials comprising 309 (8 non-advanced and 301 advanced-stage) patients with pancreatic cancer were conducted. Two to four peptides were selected among a set of 31 different peptides as vaccine candidates for personalized peptide vaccination based on human leukocyte antigen types and preexisting peptide-specific IgG levels, and subcutaneously injected. The selected peptides were subcutaneously injected. Of the 309 patients, 81 failed to complete the 1st PPV cycle due to rapid disease progression, and their median overall survival [2.1 months; 95% confidence interval (CI), 1.8-2.7] was significantly shorter than that of the remaining 228 patients (8.4 months; 95% CI, 8.4-9.9; P<0.01). ‘Immune boosting’ was defined when IgG levels before vaccination increased more than 2-fold after vaccination. Immune boosting was observed in the majority of patients with PPV irrespective of whether or not they received concomitant chemotherapy. Additionally, patients demonstrating immune boosting exhibited longer survival rates. Although the positive-response rates and peptide-specific IgG levels in pre- and post-vaccination samples differed among the 31 peptides, patients exhibiting immune boosting in response to each of the vaccinated peptides demonstrated longer survival times. Pre-vaccination factors associated with reduced clinical benefits were high c-reactive protein (CRP) levels, high neutrophil counts, lower lymphocyte and red blood cell counts, advanced disease stage and the greater number of chemotherapy courses prior to the PPV treatment. The post-vaccination factors associated with lower clinical benefits were PPV monotherapy and lower levels of immune boosting. In conclusion, pre-vaccination inflammatory signatures, rather than pre- or post-vaccination immunological signatures, were associated with reduced clinical benefits of personalized peptide vaccination (PPV) for pancreatic cancer.

• c-reactive protein
• inflammatory signatures
• overall survival
• pancreatic cancer
• personalized peptide vaccine

Peptide-based cancer vaccines have failed to provide sufficient clinical benefits in order to be approved in clinical trials since the 1990s. To understand the mechanisms underlying this failure, the present study investigated biomarkers associated with the lower overall survival (OS) among 2,588 patients receiving personalized peptide vaccination (PPV). Survival data were obtained from a database of 2,588 cancer patients including 399 patients with lung, 354 with prostate and 344 with colon cancer. They entered into phase II clinical trials of PPV in which 2 to 4 of 31 warehouse peptides were selected for vaccination on an individual patient basis based on human leukocyte antigen (HLA) class IA-types and pre-existing peptide-specific IgG levels. Higher pre-vaccination neutrophil, monocyte and platelet counts, and lower pre-vaccination lymphocyte and red blood cell counts were inversely associated with OS, with higher sensitivities in the proportions of neutrophils and lymphocytes, respectively. The most potent unfavorable and favorable factors for OS were the median percentage of neutrophils (>64.8%) or percentage of lymphocytes (>25.1%) with correlation coefficients (R²) of 0.98 and 0.92, respectively. Higher pre-vaccination levels of c-reactive protein and other inflammatory soluble factors were inversely associated with OS. Pre-vaccination peptide-specific immunity levels had no effect on OS, although lower immune boosting levels were inversely associated with OS. None of the 31 peptides was inversely associated with OS, although a few peptides were positively associated with it. On the whole, the findings of the present study suggested that pre-vaccination inflammatory signatures, but not those of post-vaccination immune induction, were associated with lower clinical benefits of PPV.

• biomarker
• peptide vaccine
• inflammatory responses
• neutrophil proportion
• lymphocyte proportion

• combination therapy
• immune checkpoint inhibitor
• immunotherapy
• metastatic-castration resistant prostate cancer
• prostate cancer

• P50 CA180995 NCI NIH HHS
• R01 CA204021 NCI NIH HHS
• R01 CA208246 NCI NIH HHS
• R01 CA212409 NCI NIH HHS

• Antigen
• Cancer immunotherapy
• Immunology
• Oncology
• T cells

• Adult
• Aged
• Antigens, Neoplasm/immunology
• Cancer Vaccines/immunology
• Computational Biology
• Disease-Free Survival
• Epitopes/immunology
• Female
• Genomics
• HLA-A2 Antigen/immunology
• Humans
• Immune System
• Immunologic Factors
• Immunophenotyping
• Immunotherapy/methods
• Inhibitory Concentration 50
• Male
• Middle Aged
• Mutation
• Neoplasm Metastasis
• Neoplasms/immunology
• Neoplasms/therapy
• Pancreatic Neoplasms/immunology
• Peptides/immunology
• Phenotype
• Polymerase Chain Reaction
• Precision Medicine/methods
• T-Lymphocytes/immunology
• Thymoma/immunology
• Thymoma/metabolism
• Translational Research, Biomedical
• Young Adult

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.

• immunotherapy
• peptide-based cancer vaccine
• prostate cancer
• survival analysis
• urothelial cancer

• CpG
• Hyaluronidase
• Immunotherapy
• Nanovaccine
• OVA
• PEI

• Biliary tract cancer
• Cholangiocarcinoma
• Gallbladder cancer
• Immune checkpoint inhibitors
• Immunotherapy

• Cancer vaccine
• immunotherapy
• personalized medicine
• phase II trial
• upper tract urothelial cancer

This randomized phase II study investigated the immunological efficacy of herbal medicines (HM) using Hochu‐ekki‐to and Keishi‐bukuryo‐gan in combination with personalized peptide vaccination (PPV) for castration‐resistant prostate cancer (CRPC). Seventy patients with CRPC were assigned to two arms; PPV plus HM or PPV alone. Two to four peptides were chosen from 31 peptides derived from cancer antigens for a s.c. injection of PPV given eight times according to the patient's human leukocyte antigen type and levels of antigen‐specific IgG titer before PPV treatment. Peptide‐specific CTL, IgG, regulatory T cells (Treg), monocytic myeloid‐derived suppressor cells (Mo‐MDSC), and interleukin‐6 (IL‐6) responses were measured before and at the eighth vaccination. Clinical outcomes were also analyzed. Combination therapy of PPV with HM was well tolerated without severe adverse events. There was no significant change in antigen‐specific IgG, CTL, Treg or clinical outcomes. Combination therapy of PPV with HM stabilized the frequency of Mo‐MDSC (1.91%–1.92%, P = 0.96) and serum levels of IL‐6 (19.2 pg/mL to 16.1 pg/mL, P = 0.63) during the treatment. In contrast, the frequency of Mo‐MDSC and levels of IL‐6 in the PPV‐alone group were significantly increased (0.91%–1.49% for Mo‐MDSC and 9.2 pg/mL to 19.4 pg/mL for IL‐6, respectively). These results suggest that the combined use of HM has the potential to prevent the immunosuppression induced by Mo‐MDSC or IL‐6 during immunotherapy. More research is needed to validate the findings of the present study.

• Herbal medicine
• immunotherapy
• personalized peptide vaccination
• phase II study
• prostate cancer

• MPLA
• codelivery
• hollow mesoporous nanoparticles
• immune response
• peptides

• Animals
• Antineoplastic Agents/chemistry
• Antineoplastic Agents/therapeutic use
• Dendritic Cells/immunology
• Hydrophobic and Hydrophilic Interactions
• Lipid Bilayers/chemistry
• Melanoma/drug therapy
• Mice
• Nanoparticles/chemistry
• Peptides/chemistry
• Silicon Dioxide/chemistry

• Cytotoxic lymphocytes
• Hepatocellular carcinoma
• Personalized peptide vaccination
• TOMO radiotherapy

• Adult
• Aged
• Bone Marrow/drug effects
• Bone Neoplasms/blood
• Bone Neoplasms/secondary
• Bone Neoplasms/therapy
• Cancer Vaccines/therapeutic use
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/pathology
• Carcinoma, Hepatocellular/therapy
• Combined Modality Therapy/adverse effects
• Combined Modality Therapy/methods
• Female
• Humans
• Liver Neoplasms/blood
• Liver Neoplasms/pathology
• Liver Neoplasms/therapy
• Lung Neoplasms/blood
• Lung Neoplasms/secondary
• Lung Neoplasms/therapy
• Male
• Middle Aged
• Neoplasm Staging
• Peptides/therapeutic use
• Peritoneal Neoplasms/blood
• Peritoneal Neoplasms/secondary
• Peritoneal Neoplasms/therapy
• Portal Vein/pathology
• Precision Medicine/adverse effects
• Precision Medicine/methods
• Radiotherapy/adverse effects
• Radiotherapy/methods
• Vaccination/adverse effects
• Vaccination/methods
• Venous Thrombosis/etiology
• Venous Thrombosis/therapy
• alpha-Fetoproteins/analysis

Overall survival of patients with hepatocellular carcinoma (HCC) refractory to locoregional therapy is dismal, even following treatment with sorafenib, a multikinase inhibitor. To develop a more efficacious treatment, we undertook a feasibility study of personalized peptide vaccination (PPV) for HCC, in which the peptides were selected from 31 peptide candidates based on the pre‐existing immunity. Twenty‐six HCC patients refractory to locoregional therapies (cohort 1) and 30 patients refractory to both locoregional and systemic therapies (cohort 2) were entered into the study. There were no severe adverse events related to PPV except for one injection site reaction. At the end of the first cycle of six vaccinations, successful CTL or IgG boosting was observed in 57% or 46% of patients in cohort 1 and in 54% or 52% of patients in cohort 2, respectively. Successful IgG boosting at the end of the second cycle was observed in the majority of patients tested. Median overall survival was 18.7 months (95% confidence interval, 12.2–22.5 months) in cohort 1, and 8.5 months (95% confidence interval, 5.9–12.2 months) in cohort 2. Based on the higher rates of immune boosting and the safety profile of PPV, further clinical studies of PPV would be warranted for patients with HCC refractory to not only locoregional therapy but also both locoregional and systemic therapies. The protocol of this study was registered with the UMIN Clinical Trials Registry (UMIN000001882 and UMIN000003590).

• Cancer immunotherapy
• hepatocellular carcinoma
• immune response
• overall survival
• personalized peptide vaccine

• cancer vaccine
• chimeric antigen receptor T cells
• immunotherapy
• prostate cancer
• tumor microenvironment

• antibody therapy
• chemotherapy
• immune checkpoint inhibitors
• immunotherapy
• lung cancer
• non-small cell lung cancer
• overall survival
• progression-free survival
• vaccine therapy

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.

• HLA-A11
• HLA-A33
• IgG
• cytotoxic T-Lymphocytes
• peptide vaccine

• Epitope spreading
• IgG
• Lck
• PPV
• SCLC

• Cancer
• Immune modulation
• Immunotherapy
• Radiobiology
• Radiotherapy

• CTL
• HIF-1α
• HLA-A24
• Peptide
• Renal cell carcinoma

Cancer vaccines aim at eliciting not only an immune response against specific tumor antigens, but also at enhancing a preexisting immunity against the tumor. In this context, we recently reported on the levels of preexisting immunity in prostate cancer patients vaccinated with the HER-2 hybrid peptide (AE37), during a phase I clinical trial. The purpose of the current study was to correlate between preexisting immunity to the native HER-2 peptide, AE36, and expression of HLA-A2 and -A24 molecules with the clinical outcome. Additionally, we investigated the ability of the AE37 vaccine to induce an antitumor immune response against other tumor associated antigens, not integrated in the vaccine formulation, with respect to the clinical response.

We analyzed prostate cancer patients who were vaccinated with the AE37 vaccine [Ii-Key-HER-2/neu_(776–790) hybrid peptide vaccine (AE37), which is a MHC class II long peptide vaccine encompassing MHC class I epitopes, during a phase I clinical trial. Preexisting immunity to the native HER-2/neu_(776–790) (AE36) peptide was assessed by IFNγ response or dermal reaction at the inoculation site. Antigen specificity against other tumor antigens was defined using multimer analysis. Progression free survival (PFS) was considered as the patients’ clinical outcome. Two-tailed Wilcoxon signed rank test at 95 % confidence interval was used for statistical evaluation at different time points and Kaplan–Meier curves with log-rank (Mantel-Cox) test were used for the evaluation of PFS.

Preexisting immunity to AE36, irrespectively of HLA expression, was correlated with longer PFS. Specific CD8⁺ T cell immunity against E75 and PSA_146–151 (HLA-A2 restricted), as well as, PSA_153–161 (HLA-A24 restricted) was detected at relatively high frequencies which were further enhanced during vaccinations. Specific immunity against PSA_153–161 correlated with longer PFS in HLA-A24⁺ patients. However, HLA-A2⁺ patients with high preexisting or vaccine-induced immunity to E75, showed a trend for shorter PFS.

Our data cast doubt on whether preexisting immunity or epitope spreading specific for HLA-class I-restricted peptides can actually predict a favorable clinical outcome. They also impose that preexisting immunity to long vaccine peptides, encompassing both HLA class II and I epitopes should be considered as an important prerequisite for the improvement of future immunotherapeutic protocols.

Protocol ID Code: Generex-06-07

National Organization for Medicines (EOF) ID Code: IS-107-01-06

NEC Study Code: EED107/1/06

EudraCT Number: 2006-003299-37

Date of registration: 07/06/2006

Date of enrolment of the first participant to the trial: Nov 1st, 2007

The online version of this article (doi:10.1186/s40425-016-0183-4) contains supplementary material, which is available to authorized users.

• Cancer immunotherapy
• Epitope spreading
• HER-2 long peptide vaccine
• Preexisting immunity
• Prostate cancer

• Cancer immunotherapy
• Carcinoma of unknown primary site
• Metastasis
• Personalized peptide vaccine
• Unfavorable subsets

• Adenocarcinoma/mortality
• Adenocarcinoma/pathology
• Adenocarcinoma/therapy
• Adult
• Aged
• Cancer Vaccines/immunology
• Carcinoma, Squamous Cell/mortality
• Carcinoma, Squamous Cell/pathology
• Carcinoma, Squamous Cell/therapy
• Cytotoxicity, Immunologic
• Drug Resistance, Neoplasm
• Epitopes, T-Lymphocyte/metabolism
• Female
• HLA Antigens/metabolism
• Humans
• Immunity, Humoral
• Immunotherapy/methods
• Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/metabolism
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasms, Unknown Primary/mortality
• Neoplasms, Unknown Primary/pathology
• Neoplasms, Unknown Primary/therapy
• Peptide Fragments/metabolism
• Precision Medicine
• Survival Analysis
• T-Lymphocytes, Cytotoxic/immunology
• Vaccination
• Vaccines, Subunit/immunology

A phase I study of a new cancer vaccine (KRM‐10), consisting of a mixture of 10 different short peptides, was conducted for patients with advanced gastrointestinal cancers. Primary or secondary endpoints included the dose‐limiting toxicity (DLT), or safety and immune responses, respectively. Peptide‐specific cytotoxic T lymphocytes (CTL) and immunoglobulin G (IgG), together with soluble inflammatory factors, were measured before and after vaccination. Twenty‐one patients were vaccinated with KRM‐10 at dose levels of 10 (n = 6), 20 (n = 8) or 30 mg (n = 7) of peptides every week for 6 weeks. No DLT were observed in the dose range evaluated. Common treatment‐related adverse events were a grade 1 injection site reaction in 15 patients, and fever in three patients (grade 1 in two patients and grade 2 in one patient). CTL activity to at least one peptide at the time of the third and sixth vaccination increased in 2 and 3 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 2 and 1 of 6 (30 mg) patients, respectively. IgG levels, at the third and sixth vaccination, were also increased in 1 and 1 of 6 (10 mg), 2 of 8 and 4 of 6 (20 mg), or 1 and 3 of 6 (30 mg) patients, respectively. The KRM‐10 vaccine consisting of 20 mg of peptides was determined as the optimal dose for a coming phase II trial because of its safety, and also for demonstrating the most potent activity for augmenting the immune response of the three doses tested. This trial was registered at the UMIN Clinical Trials Registry as UMIN000008820.

• Cancer vaccine
• cytotoxic T-lymphocytes
• human leukocyte antigen
• peptide
• phase I

• Cyclophosphamide
• Immunotherapy
• Myeloid-derived suppressor cell
• Peptide vaccination
• Phase II trial
• Regulatory T cell

• Administration, Metronomic
• Aged
• Aged, 80 and over
• Cancer Vaccines/administration & dosage
• Cancer Vaccines/adverse effects
• Cancer Vaccines/immunology
• Combined Modality Therapy
• Cyclophosphamide/administration & dosage
• Humans
• Male
• Middle Aged
• Neoplasm Grading
• Neoplasm Metastasis
• Peptides/administration & dosage
• Peptides/chemistry
• Peptides/immunology
• Precision Medicine/methods
• Prostatic Neoplasms, Castration-Resistant/immunology
• Prostatic Neoplasms, Castration-Resistant/mortality
• Prostatic Neoplasms, Castration-Resistant/pathology
• Prostatic Neoplasms, Castration-Resistant/therapy
• Survival Analysis
• T-Lymphocytes, Cytotoxic/immunology
• T-Lymphocytes, Cytotoxic/metabolism
• T-Lymphocytes, Regulatory/immunology
• T-Lymphocytes, Regulatory/metabolism
• Treatment Outcome
• Vaccines, Subunit/administration & dosage
• Vaccines, Subunit/adverse effects
• Vaccines, Subunit/immunology