Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835]

INTRODUCTION: Mucin 1 (MUC1) is a high molecular weight glycoprotein overexpressed on adenocarcinoma cells and is a target for immunotherapy protocols. To date, clinical trials against MUC1 have included advanced cancer patients. Herein, we report a trial using early stage breast cancer patients and injection of oxidized mannan-MUC1. METHOD: In a randomized, double-blind study, 31 patients with stage II breast cancer and with no evidence of disease received subcutaneous injections of either placebo or oxidized mannan-MUC1, to immunize against MUC1 and prevent cancer reoccurrence/metastases. Twenty-eight patients received the full course of injections of either oxidized mannan-MUC1 or placebo. Survival and immunological assays were assessed. RESULTS: After more than 5.5 years had elapsed since the last patient began treatment (8.5 years from the start of treatment of the first patient), the recurrence rate in patients receiving the placebo was 27% (4/15; the expected rate of recurrence in stage II breast cancer); those receiving immunotherapy had no recurrences (0/16), and this finding was statistically significant (P = 0.0292). Of the patients receiving oxidized mannan-MUC1, nine out of 13 had measurable antibodies to MUC1 and four out of 10 had MUC1-specific T cell responses; none of the placebo-treated patients exhibited an immune response to MUC1. CONCLUSION: The results suggest that, in early breast cancer, MUC1 immunotherapy is beneficial, and that a larger phase III study should be undertaken

Dendritic cells in cancer immunology and immunotherapy

Dendritic cells (DCs) are a diverse group of specialized antigen-presenting cells with key roles in the initiation and regulation of innate and adaptive immune responses. As such, there is currently much interest in modulating DC function to improve cancer immunotherapy. Many strategies have been developed to target DCs in cancer, such as the administration of antigens with immunomodulators that mobilize and activate endogenous DCs, as well as the generation of DC-based vaccines. A better understanding of the diversity and functions of DC subsets and of how these are shaped by the tumour microenvironment could lead to improved therapies for cancer. Here we will outline how different DC subsets influence immunity and tolerance in cancer settings and discuss the implications for both established cancer treatments and novel immunotherapy strategies.S.K.W. is supported by a European Molecular Biology Organization Long- Term Fellowship (grant ALTF 438– 2016) and a CNIC–International Postdoctoral Program Fellowship (grant 17230–2016). F.J.C. is the recipient of a PhD ‘La Caixa’ fellowship. Work in the D.S. laboratory is funded by the CNIC, by the European Research Council (ERC Consolidator Grant 2016 725091), by the European Commission (635122-PROCROP H2020), by the Ministerio de Ciencia, Innovación e Universidades (MCNU), Agencia Estatal de Investigación and Fondo Europeo de Desarrollo Regional (FEDER) (SAF2016-79040-R), by the Comunidad de Madrid (B2017/BMD-3733 Immunothercan- CM), by FIS- Instituto de Salud Carlos III, MCNU and FEDER (RD16/0015/0018-REEM), by Acteria Foundation, by Atresmedia (Constantes y Vitales prize) and by Fundació La Marató de TV3 (201723). The CNIC is supported by the Instituto de Salud Carlos III, the MCNU and the Pro CNIC Foundation, and is a Severo Ochoa Centre of Excellence (SEV-2015-0505).S

Polypoidal choroidal vasculopathy associated with Doyne's familial choroiditis: treatment with thermal laser

PURPOSE. To report the unusual occurrence of polypoidal choroidal vasculopathy (PCV) in a patient with Doyne’s familial honeycomb choroiditis (DFHC) and its course after laser treatment. DESIGN. Interventional case report. METHODS. Indocyanine green (ICG) angiography guided laser was performed on active polypoidal lesions. RESULTS. A 45-year-old man with a 15-year history of bilateral DFCH and a scarred macular choroidal neovascularization in the right eye (RE) was referred to us with exudative maculopathy in the left eye (LE). His best-corrected visual acuity (BCVA) was 201800 in the RE and 20140 in the LE. ICG angiography revealed a picture that was characteristic for PCV in both eyes. ICG guided argon green laser was performed on the active parapapillary and perifoveal polypoidal lesions of the LE. Eight months after the laser photocoagulation treatment, the macular exudative lesions had subsided and the BCVA improved to 20/20. The favorable anatomic and functional results have remained stable over 3 years. CONCLUSIONS. This is, to our knowledge, the first case of a PCV that occurred secondary to DFHC

Macular hole surgery with short-acting gas and short-duration face-down positioning

Tina Xirou,1 Panagiotis G Theodossiadis,2 Michael Apostolopoulos,3 A Stamatina Kabanarou,1 Elias Feretis,1 Ioannis D Ladas,3 Chrysanthi Koutsandrea31Vitreoretinal Unit, Red Cross Hospital, 2B Department of Ophthalmology, University of Athens, Greece; 3A Department of Ophthalmology, University of Athens, GreecePurpose: To report on the outcomes of vitrectomy and sulfur hexafluoride (SF6) gas tamponade for idiopathic macular holes with 2 days of face-down positioning.Patients and methods: This was a prospective, nonrandomized, observational sequential case-series study on 23 consecutive patients receiving macular hole surgery using 20% SF6 and advised to stay in a face-down position for 2 days postoperatively (SF6 group). These patients were compared to 23 consecutive patients who had previously undergone macular hole surgery, had received 14% C3F8, and were advised to maintain a face-down position for 2 days (C3F8 group). Patients in both groups underwent vitrectomy, internal limiting membrane peeling, and fluid gas exchange using either SF6 or C3F8. Preoperative and postoperative data included best corrected visual acuity recorded in LogMAR units, slit-lamp biomicroscopy, and optical coherence tomography.Results: At a 6-month follow-up, macular hole closure was noted in 23/23 eyes (100%) and in 22/23 eyes (96%) in the SF6 and C3F8 groups, respectively. The improvement in visual acuity (measured through Snellen acuity lines both preoperatively until 6 months postoperatively) was 4.08 ± 2.31 (95% confidence interval [CI]: 3.08–5.08) for the SF6 group and 2.87 ± 2.30 (95% CI: 1.87–3.86) for the C3F8 group; this difference was not statistically significant (P = 0.06).Conclusion: Vitrectomy with internal limiting membrane peeling and a short-acting gas tamponade using SF6 with posture limitation for 2 days may give a high success rate in macular hole surgery.Keywords: idiopathic macular holes, SF6 gas tamponade, C3F8 gas tamponad

Diffuse retinal pigment epitheliopathy: Treatment with laser photocoagulation

PURPOSE. To evaluate the effectiveness of laser treatment in eyes with diffuse retinal pigment epitheliopathy (DRPE). METHODS. The authors retrospectively reviewed the medical records of 56 consecutive patients (78 eyes) with DRPE. All eyes were treated with digital fluorescein angiography guided argon green laser photocoagulation, direct on the focal retinal pigment epithelium (RPE) leaks and in a grid pattern to the RPE decompensation areas. A processed digital red-free fundus image including all the important traces on it was used as a guide to the laser treatment. The follow-up period ranged from 6 months to 7 years. RESULTS. At the end of the follow-up time, 70 (89.7%) eyes showed anatomic improvement with complete or partial resolution of the macular exudative lesions. Visual acuity of less than 20140 was noted in 60 eyes (76.9%) preoperatively compared with 46 eyes (59.0%) finally (p=0.0252). The visual acuity was improved in 19 eyes (24.4%), stabilized in 51 (65.4%), and reduced in only 8 eyes (10.2%). CONCLUSIONS. In this series of patients with DRPE, the results of laser treatment were uniformly satisfactory producing a gradual resolution of the macular exudative lesions and an improvement or stabilization of the visual acuity

Cyst formation in optic disc pit maculopathy

Purpose: To evaluate the presence and the evolution of cyst formation in optic disc pit maculopathy. Methods: In this prospective study, 18 cases with optic disc pit maculopathy were studied. Five of them showed cyst formation in the fovea at the initial examination. The fundus findings were documented with slit-lamp biomicroscopy, indirect ophthalmoscopy, and stereoscopic photography of the posterior pole. All 5 patients were treated with a macular scleral buckle procedure. Results: The presence of cysts in the elevated macula depends on the grade of the disease. Cyst formation can develop not only in the later stage of the disease but also quite early. In all 5 patients cyst formation gradually decreased and finally disappeared after the surgical procedure. Conclusions: Cyst formation is an entity which accompanies the macular detachment associated with optic disc pit. The development of the cysts has been noticed after the establishment of the schisis-like separation and before or in conjunction with the formation of a lamellar macular hole which usually accompanies the optic disc pit maculopathy