The majority of peptide-based cancer vaccines under development are for human leukocyte antigen (HLA)-A2- or -A24-positive patients. To overcome this limitation, we conducted a phase I clinical study ...of peptide vaccines designed for cancer patients with six different HLA-A types. Eligible patients were required to have failed prior standard cancer therapies and to be positive for the HLA-A2, -A24 or -A3 (A3, A11, A31 and A33) supertype. Three sets of 8 candidate peptides (24 peptides in total) were provided for vaccination to HLA-A2+, HLA-A24+ and HLA-A3+ patients, respectively. Personalization of the vaccination peptides from the candidate pool was made by considering the patients' HLA types and pre-existing levels of IgGs to the candidate peptides. Seventeen patients were enrolled in this study. The peptide vaccinations were well tolerated in all patients with no vaccine-related severe adverse events. Augmentation of cytotoxic T lymphocyte (CTL) or IgG responses specific to the vaccinated peptides was observed in 11 or 10 out of 13 cases tested, respectively. This new type of vaccine is recommended for phase II clinical trial because of its tolerability and the immune responses to the vaccinated peptides.
To facilitate the development of a peptide-based cancer vaccine for prostate cancer patients, we examined whether any of the 13 peptides previously reported to induce HLA-class I-restricted cytotoxic ...T lymphocyte (CTL) activity in HLA-A3 supertype (-A3, -A11, -A31 and -A33)-positive prostate cancer patients are also capable of inducing CTLs restricted to HLA-A2, HLA-A24 or HLA-A26 alleles. Among the 13 peptides tested, a peptide at positions 309 to 318 of β-tubulin 5 exhibited binding activity to the HLA-A*2402 molecule and induced HLA-A24-restricted CTL activity against prostate cancer cells derived from peripheral blood mononuclear cells of prostate cancer patients. The CTL activity was determined to be specific to this peptide and was mediated by CD8+ T cells in an HLA-class I-restricted manner. These results suggest that this peptide could be applicable as a peptide vaccine, not only for HLA-A3 supertype-positive, but also for HLA-A24-positive prostate cancer patients.
A total of 35 patients with benign prostatic hyperplasia (BPH) were treated with the Ho: YAG laser using a new technique termed holmium laser resection of the prostate or HoLRP. The laser energy was ...applied directly to prostatic tissue exclusively through the use of a standard 550 micron end-firing fiber. A high-powered holmium laser was used and was set at 2.4 J per pulse at 25 pulses per second for an average power of 60 W. The mean preoperative AUA Symptom Score was 24. Postoperatively, the score dropped to 10.9, 8.2, 5.2, and 4.6 at 1 week, 1 month, 3 months, and 6 months, respectively. The peak urine flow rate improved from 6.3 mL/sec preoperatively to 15.1, 15.3 and 16 mL/sec at 1 week, 1 month, 3 months, and 6 months. A foley catheter was removed within 24 hours of completion of the operation in 31 patients (89%), and voiding was improved. The HoLRP technique was bloodless, and the short-term results were satisfactory. Most importantly, the defect produced by HoLRP is identical to that of a conventional transurethral resection. These initial results demonstrate that HoLRP is a useful surgical alternative in the treatment of patients with obstructive BPH.
INTRODUCTIONParaganglioma of the urinary bladder is a very rare disease accounting for 0.06% of all bladder tumors. Owing to their rarity and symptomatic variability, preoperative diagnosis is often ...difficult.CASE PRESENTATIONA 70-year-old male was referred to our department for hematuria. Cystoscopy showed a non-papillary broad-based tumor. Computed tomography and magnetic resonance imaging revealed a 32-mm bladder tumor at the top of the bladder, which suggested muscle-invasive bladder tumor. We diagnosed muscle-invasive bladder cancer or urachal carcinoma, and transurethral resection of the bladder tumor was performed. At the initiation of transurethral resection of the bladder tumor, the systolic blood pressure was elevated to over 200 mmHg. The pathological findings revealed paraganglioma of the urinary bladder, and afterward, a partial cystectomy was performed.CONCLUSIONWe herein reported the case of paraganglioma in the bladder whose blood pressure became extremely elevated during transurethral resection of the bladder tumor. In addition, we analyzed important factors for preoperative diagnosis using 162 cases reported in Japan.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
INTRODUCTIONThe safety and efficacy of combination therapy comprising immune checkpoint inhibitors and cancer-specific peptide vaccines have not yet been established.CASE PRESENTATIONA 71-year-old ...female metastatic renal cell carcinoma patient with multiple lung and pleural metastases. She had been treated with interferon alpha, sunitinib, axitinib, and pazopanib sequentially, but no clinical efficacy was observed. She participated in a clinical trial using cancer-specific peptide vaccine therapy. Initially no antitumor effect was observed, and vaccine therapy was ceased after two courses. But 3 months after the start of nivolumab, remarkable tumor shrinkage was observed at all metastatic sites, which resulted in almost complete response at 6 months. At 10 months, nivolumab was stopped due to cellulitis at the peptide vaccine inoculation site. Intriguingly, even after nivolumab discontinuation, complete response was maintained for more than 1 year.CONCLUSIONWe experienced a remarkable antitumor effect by nivolumab in a patient who was previously treated with vaccine therapy.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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