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ABSTRACTCluster of differentiation 47 (CD47) is a transmembrane protein highly expressed in tumor cells that interacts with signal regulatory protein alpha (SIRPα) and triggers a “don’t eat me” signal to the macrophage, inhibiting phagocytosis and enabling tumor escape from immunosurveillance. The CD47-SIRPα axis has become an important target for cancer immunotherapy. To date, the advancement of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hematologic toxicity including anemia. To overcome those challenges a bispecific approach was taken. CC-96673, a humanized IgG1 bispecific antibody co-targeting CD47 and CD20, is designed to bind CD20 with high affinity and CD47 with optimally lowered affinity. As a result of the detuned CD47 affinity, CC-96673 selectively binds to CD20-expressing cells, blocking the interaction of CD47 with SIRPα. This increased selectivity of CC-96673 over monospecific anti-CD47 approaches allows for the use of wild-type IgG1 Fc, which engages activating crystallizable fragment gamma receptors (FcγRs) to fully potentiate macrophages to engulf and destroy CD20+ cells, while sparing CD47+CD20− normal cells. The combined targeting of anti-CD20 and anti-CD47 results in enhanced anti- tumor activity compared to anti-CD20 targeting antibodies alone. Furthermore, preclinical studies have demonstrated that CC-96673 exhibits acceptable pharmacokinetic properties with a favorable toxicity profile in non-human primates. Collectively, these findings define CC-96673 as a promising CD47 × CD20 bispecific antibody that selectively destroys CD20+ cancer cells via enhanced phagocytosis and other effector functions.

Dry eye disease is a multifactorial condition characterised by tear film instability, hyperosmolarity and ocular surface inflammation. Understanding the epidemiology of dry eye disease and recognising both modifiable and non-modifiable risk factors can assist eye care practitioners in assessing, treating, and managing patients with the condition. This review considers current knowledge surrounding its incidence and prevalence, as well as associated demographic, systemic, ocular, and iatrogenic, and lifestyle-related modifiable risk factors. Population-based prevalence estimates vary according to the diagnostic criteria used to define dry eye disease, as well as severity and demographic characteristics of the population. Considering recent data and variable population demographics, conservative prevalence estimates suggest that 10–20% of the population over 40 years of age report moderate to severe symptoms and/or seek treatment for dry eye disease. Individuals with specific non-modifiable demographic risk factors may be at increased risk of developing dry eye disease. Advanced age, female sex and East Asian ethnicity have been identified as key non-modifiable demographic features predisposing individuals to dry eye disease. Systemic conditions that have been associated with an increased risk of dry eye disease include migraine, Sjögren syndrome, connective tissue disorders, mental health disorders, diabetes mellitus and androgen deficiency. Medications that may contribute to this risk include antidepressants, antihistamines, and hormone replacement therapy. Ocular and iatrogenic risk factors of dry eye disease include blepharitis, Demodex infestation, ocular surgery, blink completeness, contact lens wear, and topical ophthalmic medications. A range of modifiable lifestyle factors that can increase the risk of dry eye disease have also been identified, including low humidity environments, digital screen use, quality of sleep, diet, and eye cosmetic wear. Dry eye is a common disease affecting millions globally. Increasing knowledge regarding its associated risk factors can better prepare the eye care practitioner to successfully manage patients with this ocular surface disease.