Currently, peptide-based cancer vaccines are being developed by many different groups, however, sufficient clinical outcomes have not yet been obtained. We have developed a personalized peptide vaccine for advanced cancer patients with different types of HLA-A locus. Personalization of the vaccination peptides from the candidate peptide pool was conducted by considering the HLA type of the patient and pre-existing levels of IgG for the candidate peptides. The personalized peptide vaccine for patients with hormone-refractory prostate cancer has been approved as an innovative therapy by the Ministry of Health, Labour and Welfare, Japan. Here, we describe the recent progress of the personalized peptide vaccine for patients with advanced cancers.

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Cancer immunotherapy is expected to be the fourth treatment against cancer. OK-432 (Picibanil^®), which is dry mycelia of hemolytic streptococcus, PSK (Krestin^®), which is a protein-bound polysaccharide obtained from basidiomycetes, and Lentinan^®, which is polysaccharide from shiitake, are administered as anti-cancer agents. However, even when administered, patients only gain increased non-specific immunity; there is no selective attack on cancer cells. On the other hand, the peptide vaccine, which we started as a new medication for cancer vaccine therapy in this study, increases only specific anti-tumor lymphocytes which can attack only cancer cells very selectively. We report on our cancer peptide vaccine therapy against oral cancer.

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Survivin, an inhibitor of apoptosis protein (IAP), is abundantly expressed in most malignancies, but is hardly detectable in normal adult tissues. We previously reported that survivin was an ideal cancer antigen, and that the survivin-2B-derived peptide, survivin-2B80-88 (AYACNTSTL), could induce a cytotoxic T lymphocyte (CTL) response in the context of HLA-A24. Based on these findings, to assess its safety and efficacy, in September 2003 we performed a clinical trial using the peptide alone on patients with advanced or recurrent oral cancer. Vaccinations were administered six times at 14-day intervals. The results indicated that survivin-2B peptide vaccination was safe and had therapeutic potential for oral cancer patients. A subsequent clinical trial of the peptide in combination with incomplete Freund's adjuvant (IFA) and interferon (IFN)-α was commenced in September 2006. The survivin-2B peptide plus IFA vaccination was administered four times at 14-day intervals in combination with IFN-α, which was administered once or twice a week. To date, no severe adverse events have been observed. The results of this trial suggest that the survivin-2B peptide and IFA vaccination in combination with IFN-α induced the peptide specific CTL more effectively than the peptide alone, and that the vaccination was tolerated well by patients. This regimen may be useful as a new therapeutic modality for patients with oral cancer.

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Accumulated evidence suggests the possibility that dendritic cell (DC)-based vaccination may be effective against advanced malignancies including oral cancer refractory to standard treatments.
To generate a DC vaccine which might be sufficient for cancer therapy, first, the DCs must be appropriately matured. We have previously reported that streptococcal immunopotentiator OK-432 is able to mature DCs, and that OK-432-treated DCs stimulate T cells to kill cancer cells specific for cancer antigens, and elicits anti-tumor effect in tumor-bearing mice. Second, antigens that might not escape from the host immune system must be used for the vaccine. Identification of such cancer antigens is now progressing.
We have investigated the anti-tumor effect of DC vaccine in oral cancer patients in both prospective and retrospective clinical trials, and have obtained results strongly suggesting that DC vaccine may be safe and effective in patients with advanced oral cancer refractory to standard treatment. We should gather evidence of the anti-tumor effects of DC vaccine in further clinical trials in order for the vaccine to become the standard therapy for malignancies including oral cancer.

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We investigated the treatment outcome of 31 patients (stage II: 5, III: 7, IV: 19) who had enforced superselective intra-arterial infusion with cisplatin (50 mg/week) for 3-4 weeks and concurrent radiotherapy (total dose: 40-60 Gy) (RADPLAT) for head and neck squamous cell carcinoma from December 2003 to January 2009. The mean age of the patients was 65.9 years, ranging from 40 to 82 years. Intra-arterial infusion was performed once a week by Seldinger's method. In primary tumors, the response rate was 100%, and the complete response rate was 71.0%. In cervical lymph node metastasis of level I and II, the complete response rate was 92.6%. The survival rate in each location was 79.5%, 83.3%, 60.0% and 66.7% in the tongue, oral floor, upper and lower gingival carcinoma, respectively. Out of 18 cases histopathologically examined, 10 cases demonstrated a cytological effect of grade III or more in the classification of Ohoshi and Shimosato. Among them, 9 cases were tongue and oral floor carcinoma.
Although 3 patients showed grade 3 mucositis and 17 patients showed grade 3 or more leucopenia as toxicities, all patients were able to complete the scheduled treatments. Therefore, RADPLAT is a superior treatment method for head and neck squamous carcinoma, and is suggested to be useful for organ preservation as a treatment method for tongue and oral floor carcinoma and cervical lymph node metastasis of level I and II.

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Oral mucositis is a dose-limiting toxicity in cancer chemotherapy. However, at present, no effective prophylaxis or treatment for oral mucositis has been established in Japan. In USA and Europe, incidents of chemotherapy-induced mucositis have been treated by topical oral G-CSF (Granulocyte-colony stimulating factor). We report that we have produced a topical oral G-CSF mouth rinse for use in the treatment of oral mucositis in Japanese cancer patients. The subjects were 6 patients with solid tumors, including oral cancer and leukemia, who had developed chemotherapy-induced mucositis. G-CSF (filgrastim) was administered as a mouth rinse (carboxymethylcellulose 2%) at a dose of 4 × 75μg/day for 5 days in relation to severe mucositis (NCI-CTCAEv3.0 grade 3 or 4).
Result: Severe mucositis was reduced significantly and both eating difficulties and oral pain were improved. In conclusion, a topical oral G-CSF mouth rinse may be beneficial in reducing oral mucositis and improving the quality of life.

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Most tongue carcinomata arise on the lateral border and sublingual surface; carcinoma of the tongue dorsum is exceedingly rare. We report a case of squamous cell carcinoma of the tongue dorsum treated with superselective intra-arterial infusion via bilateral superficial temporal arteries and daily concurrent radiotherapy.
An 80-year-old man with a mass on the left tongue dorsum was referred to our department. The mass was peduncled; the tumor size including the anterior induration of the tongue dorsum was 49 × 30 × 12 mm. After a tumor biopsy, the lesion was diagnosed as squamous cell carcinoma. No evidence of cervical lymph node metastasis was present. Retrograde superselective intra-arterial chemoradiotherapy was planned to avoid oral dysfunction after reconstructive surgery for advanced tongue carcinoma. Superselective intra-arterial chemotherapy using docetaxel (10 mg/m²/week, total 96 mg/body) and cisplatin (5 mg/m²/day, total 240 mg/body) via the bilateral superficial temporal arteries combined with daily concurrent radiotherapy (2 Gy/day, total 60 Gy) was performed for six weeks. The patient has been free of recurrence and metastasis for 25 months.

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Actinomycosis is an inflammatory disease caused by Actinomyces (oral commonly existing bacterium); the head and neck region is one of its favorite sites. We present a case of left submandibular mass after operating on tongue cancer, which was a histopathologically epidermoid cyst with Actinomyces israelii, where we excised the mass under general anesthesia. Before the operation, we suspected that the mass was likely to be a neck recurrence of the tongue cancer, since positron emission tomography (PET) indicated the standardized uptake value to be 9.9 and both computed tomography (CT) and magnetic resonance images also showed a suspicion of neck recurrence of the tongue cancer.
In the literature, chronic Actinomycosis shows mild inflammation and also enhanced CT and PET images that are similar to those of malignant tumors. When enhanced CT or PET images are observed, suspecting malignant tumors, a chronic mild inflammatory disease like actinomycosis is also one of the differential diagnoses.

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It has been reported that there is an increased incidence of head-and-neck cancer among human immunodeficiency virus (HIV) positive patients. Treatment of these patients poses difficult management challenges, because their underlying HIV infection can markedly increase morbidity associated with active cancer treatments. However, there are few reports in the literature discussing treatment options for head-and-neck cancer in HIV-positive patients. Here, we report our experience with the treatment of tongue carcinoma that arose in an HIV-positive patient.
A patient in his forties was referred to our hospital seeking treatment for right tongue carcinoma (SCC, T2N0M0). The patient was found to be HIV-positive by a routine preoperative screening blood test. His viral load was low (3400 copies/ml) and CD4 count high (527/μl). The patient underwent partial glossectomy and free skin grafting. Six months after the first surgery, late lymph node metastases were evident. The patient underwent additional radical neck dissection followed by postoperative radiotherapy (1.8 Gy/day, total 63 Gy fractions during 10 weeks). These treatment options were successfully applied without any remarkable side effects or increased morbidity related to the HIV infection. There is no evidence of recurrence or distant metastasis 7 years after the initial treatment.

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