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We report a case of posterior scleritis masquerading as choroidal melanoma following COVID-19 vaccination. An 86-year-old Caucasian male presented to a retina specialist with a 2-month history of blurred vision and pain right eye (OD). He received his fourth dose of the Pfizer-BioNTech COVID-19 vaccine before developing ocular symptoms. An intraocular mass was found OD and he was referred to our Ocular Oncology Service for potential choroidal melanoma with exudative retinal detachment. On examination, there was a 360-degree episcleral injection and no evidence of choroidal mass OD. Multimodal imaging confirmed no abnormality. Previous ultrasonography demonstrated an echolucent choroidal mass, likely representing choroidal effusion and minimal episcleral Tenon’s edema, suggesting posterior scleritis with spontaneous resolution over 1 week. Posterior scleritis following COVID-19 vaccination can masquerade as choroidal melanoma. In our case, the scleritis resolved spontaneously with no treatment and minimal consequences.

Objectives To determine clinical features and outcomes of posterior scleritis masquerading as uveal melanoma following vaccination against COVID-19 and/or COVID-19 infection. Subjects/Methods: All patients with posterior scleritis referred to our service to rule out intraocular tumor between February 2021 and June 2022, who previously had COVID-19 vaccination and/or infection (n = 8). A retrospective detailed review of patient charts and imaging was carried out. Results Previous COVID-19 vaccination was documented in 6 patients (75%) and previous COVID-19 infection and vaccination in 2 patients (25%). Demographic features included mean age of 59 years (median 68, range 5–86 years), white race (n = 7, 87%), and male sex (n = 5, 63%). Mean visual acuity at presentation was 0.24 LogMAR (median 0.18, range 0.0-0.70). The main presenting symptom was blurred vision with pain (n = 5, 63%). Features that suggested scleritis and not uveal melanoma included pain (n = 6, 75%), anterior scleritis (n = 3, 38%), disc edema (n = 1, 13%), choroidal detachment (n = 3, 38%), choroidal folds (n = 3, 38%), diffusely thickened scleral wall on ultrasonography (n = 2, 25%), Tenon’s edema (n = 5, 63%), and scleral nodule with medium/high internal reflectivity on ultrasonography (n = 4, 50%). Follow-up information at mean of 2 months (range 0.25-7 months) revealed visual acuity at date last seen was mean 0.30 LogMAR (median 0.29, range 0.0-0.54). By 2 months, resolution of “tumor” was noted in 5/6 (83%) patients with follow-up. Conclusions Posterior scleritis following COVID-19 vaccination and/or infection can masquerade as choroidal melanoma. At 2 months duration, partial or complete resolution of features with minimal visual consequence was noted.

CD3-bispecifics are antibody-based therapies that can simultaneously bind to a tumor cell surface antigen and T cells to establish a synapse between the tumor and T cell and activate T cell to induce specific killing of the tumor cell. CD3-bispecifics have demonstrated clinical success in B cell acute lymphoblastic leukemia and follicular lymphoma with approvals of that blinatumomab and mosunetuzumab that target B cell lineage antigens CD19 and CD20, respectively. However, clinical progress in deploying CD3-bispecifics for positive patient outcomes in solid tumors has been slow, due to tumor microenvironmental factors such as induction of T cell exhaustion, as well as the potential of CD3-bispecifics to mediate T cell anergy and dysfunction in the absence of adequate co-stimulation. Here we describe the development and preclinical validation of the EVOLVE platform, a tumor-targeted biologic that induces the formation of a synthetic synapse that simultaneously activates the T cell receptor complex and the CD2 receptor to optimize CD8 T cell effector phenotype and improve tumor cell killing ex vivo and in vivo, compared to matched CD3-bispecifics. We demonstrate that CD2 co-stimulation is superior to other forms of T cell co-stimulation in its ability to promote cytolytic co-stimulation, T cell cytokine production and T cell expansion. Furthermore, CD2 receptor expression is markedly elevated in tumor infiltrating lymphocytes across a broad set of tumor types, relative to the CD28 and 4-1BB costimulatory receptors. EVOLVE-mediated T cell activation is conditionally dependent on tumor antigen binding and can be tuned to promote optimal co-stimulation without increasing cytokine release relative to matched CD3-bispecifics. We also demonstrate the modular nature of the EVOLVE platform across diverse solid tumor antigens including B7H4 (VTCN1), and a novel squamous tumor antigen ULBP2. Our data highlight the broad applications of the EVOLVE platform to improve CD8 T cell-mediated anti-tumor immunity and suggest its potential as an emerging, first-in-category immunotherapeutic strategy to address unmet medical needs in oncology. Citation Format: Mandy Shu Shien Chin, Mohosin Sarkar, Eric Tam, Abudukadier Abulizi, Guixian Jin, Xingyue An, Evelyn Teran, Danielle M Klaskin, Nana Adjoa Pels, Maria Hackett, Oksana A Sergeeva, Hayden Karp, Julio Rodriguez, Sonali Dhindwal, Changqing Yuan, Zengzu Lai, Jennifer Zeiger, Amber Fearnley, Louis Matis, Jay Fine, Jeremy S Myers. EVOLVE: A novel costimulatory T cell engager platform engineered for the treatment of solid tumors [abstract]. In: Proceedings of the AACR Special Conference: Tumor Immunology and Immunotherapy; 2022 Oct 21-24; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(12 Suppl):Abstract nr B44.