Follow-up rates for patients needing regular intravitreal therapy in rural north-western Western Australia.

INTRODUCTION: Regular intravitreal injections are an important treatment for significant vision impairment caused by diabetic macular oedema. Barriers to intravitreal treatment for rural Australian patients include travel time to appointments, especially as patients face a high volume of other medical appointments for their diabetes and related co-morbidities. This audit addresses intravitreal injection compliance by identifying patients lost to follow up in north-western Western Australia. METHODS: A retrospective audit of all injections was performed in the Pilbara and Kimberley between January and December 2018. Outcome measures included total injections, number of injection patients, rates of patients lost to follow-up by region, Aboriginal and Torres Strait Islander status and diagnosis. The audit was extended to include the first 6 months of 2019 to ensure further treatment plan timeframes had lapsed. RESULTS: A total of 140 patients received injections, resulting in 346 injections. Ten patients were excluded due to relocation to another region and three patients were deceased. Seventeen patients were lost to follow-up (12.1%). Of those lost to follow-up, 14.3% were in the Pilbara region and 10% in the Kimberley region. Similar rates with respect to Indigenous status with 12.6% identifying as Aboriginal and 11.4% not. 15.8% were treated for diabetic macular oedema and 3.8% for age-related macular degeneration. CONCLUSION: The logistics of providing appropriate intravitreal therapy, including scheduling timely visits and working in hospital and community-controlled settings, requires a specific focus on those needing intravitreal treatment. The study highlights the importance of coordination and systems to enable patients to receive injections in remote settings. Further analysis of optimal patient management plans for appropriate frequency and treatment outcomes is required.

PAX8 lineage-driven T cell engaging antibody for the treatment of high-grade serous ovarian cancer.

High-grade serous ovarian cancers (HGSOC) represent the most common subtype of ovarian malignancies. Due to the frequency of late-stage diagnosis and high rates of recurrence following standard of care treatments, novel therapies are needed to promote durable responses. We investigated the anti-tumor activity of CD3 T cell engaging bispecific antibodies (TCBs) directed against the PAX8 lineage-driven HGSOC tumor antigen LYPD1 and demonstrated that anti-LYPD1 TCBs induce T cell activation and promote in vivo tumor growth inhibition in LYPD1-expressing HGSOC. To selectively target LYPD1-expressing tumor cells with high expression while sparing cells with low expression, we coupled bivalent low-affinity anti-LYPD1 antigen-binding fragments (Fabs) with the anti-CD3 scFv. In contrast to the monovalent anti-LYPD1 high-affinity TCB (VHP354), the bivalent low-affinity anti-LYPD1 TCB (QZC131) demonstrated antigen density-dependent selectivity and showed tolerability in cynomolgus monkeys at the maximum dose tested of 3 mg/kg. Collectively, these data demonstrate that bivalent TCBs directed against LYPD1 have compelling efficacy and safety profiles to support its use as a treatment for high-grade serous ovarian cancers.

A novel method to determine residual detergent in biological samples post endotoxin reduction treatment and evaluation of strategies for subsequent detergent removal.

Endotoxin removal using detergent washes and extractions are well-established, efficient, and cost-effective methods; however, removing residual detergent post treatment has been shown to be a challenge. In this communication, we show a simple and fast method for determining the detergent concentration in a protein solution post treatment and highlight strategies for detergent removal to achieve levels below the critical micelle concentration (CMC), the minimum concentration at which detergent micelles form.