CD8+ T-cell clones specific for the 5T4 antigen target renal cell carcinoma tumor-initiating cells in a murine xenograft model.

The tumor antigen 5T4 is frequently expressed at high levels on renal cell carcinoma (RCC) and other epithelial carcinomas. Surveys of normal tissues demonstrate abundant 5T4 expression on placental trophoblast cells with limited expression elsewhere. 5T4 is the target for a therapeutic cancer vaccine (MVA-5T4) that elicits 5T4-specific serological, proliferative, and cytotoxic T lymphocyte (CTL) responses. However, the antitumor activity of 5T4-specific CTL has not been extensively characterized. CD8 T cells from HLA-A2 healthy donors (n=4) or RCC patients (n=2) were stimulated in vitro with the HLA-A2-binding nonamer peptides 5T417-25 or 5T497-105 and screened by flow cytometry with specific tetramers (TET). CD8/TET T-cell clones specific for 5T417-25 or 5T497-105 peptide were isolated from 4/6 and 1/4 donors, respectively. A subset of clones specific for 5T417-25 was cytolytic for MVA-5T4-infected HLA-A2 EBV-transformed lymphoblastoid cell line target cells and for constitutively HLA-A2-expressing and 5T4-expressing RCC tumor cell lines (including A498 RCC). In a xenoengraftment assay, the coinoculation of a representative 5T417-25-specific CTL clone with A498 RCC tumors cells into immune-deficient mice completely prevented growth of A498 tumors. Taken together, these data demonstrate high-avidity CD8 CTL able to recognize the naturally processed 5T417-25 epitope on RCC tumor cells including putative tumor-initiating cells are present in peripheral blood of both healthy donors and RCC patients. CD8T-cell immunity targeting 5T417-25 is therefore of substantial interest both as a potential target for further development of vaccination or adoptive cellular immunotherapy and for immune monitoring studies in association with nonspecific immunotherapies.

[Patient with recurrent central serous chorioretinopathy who developed multiple evanescent white dots and serous retinal detachment immediately following bevacizumab administration].

BACKGROUND: A patient developed choroidal neovascularization (CNV) in one eye during treatment for bilateral recurrent central serous chorioretinopathy (CSC) and was intravitreously injected with bevacizumab; she developed multiple evanescent white dots and serous retinal detachment(SRD). CASE: A 50-year-old women had a history of CSC OD at the age of 29 years. On initial examination, CSC OD was noted, and multiple detachments of the retinal pigment epithelium OU were observed. While the CSC in the right eye was successfully treated by laser photocoagulation, it spread to both eyes following this episode. Examination of the right eye by optical coherence tomography (OCT) following the recurrence of the CSC showed slight elevation of the retinal pigment epithelial layer in the central fovea, but this finding disappeared with the resolution of the CSC. However, as the CSC combined with CNV (Gass type 2) recurred within 1 year, the patient was intravitreously injected with bevacizumab. On the day following the injection, SRD OD occurred, and on the 7th day following the injection many white lesions varying in size appeared in the deep layer of the retina, but they healed 3 weeks later, leaving only the CNV. The CNV was cured later by additional photodynamic therapy. CONCLUSION: Since the lesions of the fundus observed immediately after the bevacizumab administration resolved spontaneously without sequelae, they were retrospectively diagnosed as a white dot syndrome-like disease. The white dot syndrome-like disease is suggested as a rare complication of bevacizumab.

[A case of frosted branch angiitis associated with retinal vein occlusion as a complication of familial Mediterranean fever].

BACKGROUND: Familial Mediterranean fever (FMF) is characterized by recurrent episodes of fever and serositis caused by autosomal recessive inheritance MEFV gene mutations. It is reported that the onset of angiitis is high among patients with this disease, but no reports were found in the field of ophthalmology in Japan. In this paper, we report one case that developed from optic disc vasculitis to frosted branch angiitis associated with retinal vein occlusion. CASE: A 39 year old male. Fever, abdominal pain and chest pain were continued from childhood. In 2006, an idiopathic fever was reported with a renal disorder. Based on the results of laboratory examinations, he was diagnosed with FMF and started oral colchicines to stabilize the symptoms. In October 2007, he complained of blurry vision in his left eye that lasted for about one week prior to his visit and decided to visit our department for an examination. Visual acuity was right 1.5 and left 1.2. Although no abnormalities were found in the anterior chamber or optic media of either eye, the left eye papilla was reddish and swollen, and varicose enlargement of the retinal veins and a small retinal hemorrhage were found. Four days later, a white vascular infiltration spread to all branches of the retinal veins at the upper-half of the left eye papilla, the hemorrhage increased in the entire retina and the visual acuity decreased to 0.1. He was hospitalized and systemic administration of an antiviral agent, an antibacterial agent and a steroidal agent (prednisolone 60 mg/day) was started. Subsequently, the left eye ocular fundus findings slowly improved and he was cured 7 months later with a visual acuity of 1.0. CONCLUSION: Frosted branch angiitis may occur with systemic gene abnormalities as an underlying condition and it is important in the future to consider FMF as a causative disease.

[A suspected case of orbital mucormycosis].

BACKGROUND: This is a report on a case of suspected orbital mucormycosis after hematological examination, for whom local administration of antifungal drugs was markedly effective. CASE REPORT: A 65-year-old male developing phlegmon of the left orbit was seen at our clinic. Computed tomography revealed increased density of soft tissues and swollen external rectus muscle without any shadow of a tumor mass. The lesion was not responsive to the drip infusion of imipenem, or to oral administration of nonsteroid preparations, or to instillation of antibacterial drugs. Serum IgE levels were high, and it was suspected that the patient had orbital mycosis. After switching medication to fluconazole, injection and edema of the bulbar conjunctiva worsened, and a cable-shaped mass was palpable in the inferior margin of the orbit. Later, serum Mucor IgE antibody was found to be positive, so the patient was suspected to have mucormycosis. Medication was changed to a frequent instillation of Amphotericin B. Since edema of the bulbar conjunctiva improved, injection of the same drug under the Tenon's capsule was also given. One month after the hospital stay, the inflammatory findings of the left eye disappeared with a decrease in serum IgE levels and serum Mucor antibody. CONCLUSIONS: In cases where orbital mucormycosis is suspected, cure may be expected even by the local administration of Amphotericin B if the inflammation is localized in the anterior part of the orbit. In this disease, it is possible that examination of serum IgE and serum Mucor IgE antibody is useful for diagnosis and assessment of the clinical effects.

[The long-term outcome of trabeculectomy in advanced glaucoma].

PURPOSE: We evaluated retrospectively the surgical outcome of trabeculectomy in patients with advanced glaucoma. METHODS: We studied 18 eyes of 18 patients with advanced glaucoma (mean age: 71.2 years, mean follow-up period: 41.1 months). In each eye, the visual field was at stage 5 of Aulhorn-Greve's classification before surgery. RESULTS: Two eyes showed extreme hypotony (< 2 mmHg) 3 days after surgery and lost the central visual field permanently. Another 2 of 4 eyes which could not be maintained below 15 mmHg showed a worsening of visual field disturbance within stage 5 of Aulhorn-Greve's classification. The final visual acuity was 0.7 or better in 9 eyes (50.0%), 0.1 or worse in 2 eyes (11.1%). The final intraocular pressure (IOP) was below 10 mmHg without and with medication in 8 eyes (44.4%) and 2 eyes (11.1%) respectively. The final IOP was below 15 mmHg without and with medication in 11 eyes (61.1%) and 3 eyes (16.7%) respectively. Postoperative complications were observed in 4 eyes (22.2%). CONCLUSIONS: The cause of postoperative central visual field worsening was associated with extreme intraocular hypotony (2 mmHg) rather than IOP elevation due to bleb dysfunction. This surgery may be effective as 14 eyes (78%) were able to maintain visual acuity and the central visual field.