(525c) Nanoallergens: A Liposomal Diagnostic Platform for Platinum-Based Drug Allergies

Platinum-based antineoplastic agents, also known as platins, are the most commonly used chemotherapeutic drugs for the treatment of various cancers. Despite their usefulness in treating many cancers, it has been reported that a higher population of cancer patients undergoing platinum based chemotherapy has suffered from drug hypersensitivity reactions (DHR) following the treatments. Specifically, frequent doses of oxaliplatin and carboplatin result in a high rate of IgE-mediated DHR, resulting in more severe and detrimental allergic reactions. Currently, there is a severe lack of predictive diagnostic tools mainly because platinum-based drugs reduce the number of basophils and plasma cells due to myelosuppression effects so that specific IgE level measuring and basophil testing become less useful. Therefore, it is important to have a predictive diagnostic for drug allergies to monitor the patient during treatment. Here, we propose a nanoparticle-based liposomal diagnostic platform which we call nanoallergen to accurately diagnose and predict oxaliplatin and carboplatin drug allergies. Nanoallergen is a synthetic liposomal allergen that multivalently presents metabolites of oxaliplatin and carboplatin to facilitate crosslinking of IgE-FcεRI complex, inducing degranulation responses in a similar manner of physiological allergic responses. In order to investigate the feasibility of our design for diagnosis of platinum drug allergies, we performed in vitro cellular degranulation assays on human FcεRI-expressing RBL-SX38 using oxaliplatin and carboplatin displaying nanoallergens with 7 clinical samples taken from platin allergic subjects. The results showed that significant degranulation responses were triggered by the oxaliplatin and carboplatin presenting nanoallergens at as low as 250 pM as compared to non-platinum drug allergic patient samples. Overall, the results suggest that nanoallergens lead to the high likelihood of success in diagnosis of platinum-based drug allergies by overcoming current diagnostic limitations.