Targeting GD2 after allogeneic SCT: effector cell composition defines the optimal use of ch14.18 and the bispecific antibody construct NG-CU (GD2-CD3).

We investigated whether T cell-recruiting bispecific anti-CD3/GD2 antibody NG-CU might be an alternative to therapeutic anti-GD2 monoclonal antibody (mAb) ch14.18, mediating complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) through natural killer (NK) cells for immunotherapy in high-risk/relapsed neuroblastoma after autologous/allogeneic stem cell transplantation (auto/alloSCT). Different antibody concentrations and effector-to-target ratios (E:T) were evaluated using xCELLigence RTCA system, peripheral blood mononuclear cells (PBMCs) (healthy donors and patients after alloSCT), and neuroblastoma cell lines (LS/LAN-1). Mean specific lysis of LS cells utilizing PBMCs from healthy donors and ch14.18 (1 µg/ml) was 40/66/75% after 12/24/48 h compared to 66/93/100% in the presence of NG-CU (100 ng/ml). NG-CU showed enhanced cytotoxicity compared to ch14.18, even at lower concentrations and E:T ratios, and completely eradicated LS cells after 72 h. To decipher the influence of effector cell subsets on lysis, different ratios of T and NK cells were tested. At a ratio of 1:1, ch14.18 was more effective than NG-CU. Using patient PBMCs taken at different time points posttransplant, significant lysis with both constructs was detectable depending on percentages and total numbers of T and NK cells; in the early posttransplant phase, NK cells were predominant and ch14.18 was superior, whereas later on, T cells represented the majority of immune cells and NG-CU was more effective. Our study highlights the importance of analyzing effector cell subsets in patients before initiating antibody-based therapy. Consequently, we propose an adjusted administration of both antibody constructs, considering the state of posttransplant immune recovery, to optimize anti-tumor activity.

Involvement of the Anterior Segment of the Eye in Patients with Mucopolysaccharidoses: A Review of Reported Cases and Updates on the Latest Diagnostic Instrumentation.

Mucopolysaccharidoses (MPS) are a heterogeneous group of rare inherited disorders, characterized by the lack or malfunction of lysosomal enzymes necessary for glycosaminoglycan (GAGs) catabolism, and their subsequent accumulation in many tissues and organs throughout the body. An overview of the current knowledge of corneal and anterior segment manifestations in patients with MPS was provided and clinical guidelines for their diagnosis and management were furnished. The anterior segment of the eye is usually involved in every subtype of MPS, with major complications including varying degrees of corneal opacification and raised intraocular pressure (IOP) with development of glaucoma. Their recognition and management can be very useful in the diagnosis of MPS. Novel techniques are available to objectively measure the grade and extent of corneal clouding and give information about the anatomy of the anterior chamber and the structures of the angle beyond the clouded cornea. It is advisable to take advantage of this new instrumentation in order to obtain thorough information on the ocular involvement and its related anterior chamber complications for a better management of patients with MPS, both in terms of visual prognosis and therapeutic outcome.

Cytomegalovirus anterior uveitis: long-term follow-up of immunocompetent patients.

BACKGROUND: We aimed to report on the clinical findings and long-term prognosis of patients with cytomegalovirus (CMV) anterior uveitis. METHODS: This was a retrospective observational study on 15 immunocompetent patients with CMV anterior uveitis and a follow-up longer than 24 months (mean: 62.1 ± 28.5 months). RESULTS: Uveitis was unilateral and hypertensive in all cases, with acute relapsing having the characteristics of Posner-Schlossman syndrome in nine (60 %) and chronic in nine patients (40 %), three of whom were clinically classified as Fuchs' heterocromic iridocyclitis (20 %). All patients received topical antiviral and corticosteroid therapy, with six patients also receiving systemic therapy with valganciclovir or acyclovir. The mean number of uveitis relapses significantly decreased, before and after anti-CMV therapy, from 0.23 ± 0.17 to 0.03 ± 0.03 (p < 0.001), without significant differences among patients treated with topical therapy alone or combined topical and systemic therapy. Cataracts developed in nine out of 13 patients (69.2 %). A chronic raise in intraocular pressure (IOP) was found in 13 patients (86.6 %), with nine requiring surgery (60 %). At the end of the follow-up, all patients had a quiescent uveitis, with ten of them requiring topical low dose steroid therapy (66.6 %) and combined with systemic acyclovir in four cases. Eight patients (53.3 %) were on antiglaucomatous therapy. The last mean IOP value was 14.9 ± 3.6 mmHg (range 8-21 mmHg), and visual acuity was 0.89 ± 0.21. CONCLUSIONS: CMV-associated anterior uveitis has a fairly good long-term visual prognosis. Antiviral therapy can reduce the frequency of relapses, but cataracts and a chronic raise in IOP are frequent complications often requiring a surgical approach.