IL-15/IL-15Rα-Fc-Fusion Protein XmAb24306 Potentiates Activity of CD3 Bispecific Antibodies through Enhancing T-Cell Expansion.

An insufficient quantity of functional T cells is a likely factor limiting the clinical activity of T-cell bispecific antibodies, especially in solid tumor indications. We hypothesized that XmAb24306 (efbalropendekin alfa), a lymphoproliferative interleukin (IL)-15/IL-15 receptor α (IL-15Rα) Fc-fusion protein, may potentiate the activity of T-cell dependent (TDB) antibodies. The activation of human peripheral T cells by cevostamab, an anti-FcRH5/CD3 TDB, or anti-HER2/CD3 TDB resulted in the upregulation of the IL-2/15Rβ (CD122) receptor subunit in nearly all CD8+ and majority of CD4+ T cells, suggesting that TDB treatment may sensitize T cells to IL-15.

IMiDs Augment CD3-Bispecific Antibody-Induced CD8+ T-Cell Cytotoxicity and Expansion by Enhancing IL2 Production.

Although CD3-bispecific antibodies have shown promising activity in the treatment of hematological cancers, insufficient T-cell costimulation may limit long-term responses. Immunomodulatory drugs (IMiDs), routinely used in treating multiple myeloma, possess pleiotropic antimyeloma properties and have been described to enhance T-cell responses similar to costimulatory signaling and may therefore have synergistic effects when combined with T-cell bispecifics. In this report, we demonstrate that IMiDs substantially enhance tumor cell killing induced by CD3 bispecifics and increase CD8+ T-cell proliferation and expansion.

Anti-LYPD1/CD3 T-Cell-Dependent Bispecific Antibody for the Treatment of Ovarian Cancer.

Ovarian cancer is a diverse class of tumors with very few effective treatment options and suboptimal response rates in early clinical studies using immunotherapies. Here we describe LY6/PLAUR domain containing 1 (LYPD1) as a novel target for therapeutic antibodies for the treatment of ovarian cancer. LYPD1 is broadly expressed in both primary and metastatic ovarian cancer with ∼70% prevalence in the serous cancer subset.

Successful Reduction of Intraocular Pressure in a Patient with Glaucoma Secondary to Sturge-Weber Syndrome Using a Suprachoroidal Shunt.

Aim: We present a case of successful reduction of intraocular pressure (IOP) in a patient with Sturge-Weber syndrome (SWS) and moderate open angle glaucoma using a suprachoroidal shunt.

Background: Patients with SWS glaucoma often have elevated episcleral venous pressure resulting in elevated IOP. This makes the conventional pathway for aqueous humor outflow a poor target for IOP reduction, yielding it difficult to treat.

Prompt vitrectomy for management of endophthalmitis in setting of unexposed glaucoma drainage implant.

Purpose: To highlight a rare case of fulminant endophthalmitis in the late post-operative stage after glaucoma drainage device implantation without evidence of device exposure, and to share the unique management that resulted in successful restoration of vision and intraocular pressure control.

Observations: Endophthalmitis after glaucoma drainage implantation (GDI) is a rare complication most often associated with exposure of the device. Management options are limited, but removal of GDI is a common approach in the setting of an exposed implant.