Abstract 1736: Local treatment of lung cancer by inhaled monoclonal antibodies: A pre-feasibility screening approach for spray drying

Abstract Local treatment of asthma and COPD by inhaled therapies has been standard of care for decades. A similar approach for lung cancer treatment could bring many benefits to the patient, including ease of administration, non-invasiveness, and potential for reduced side effects. Spray drying is a versatile, scalable manufacturing technique used to engineer therapies for delivery to the lung by dry powder inhaler. It is applicable to nearly all classes of molecules, including RNA, small molecules and proteins. Spray dried inhalation powders eliminate the need for cold chain storage, and can improve product shelf life compared with liquid formulations, improving access for developing nations and rural populations. Recently, inhaled delivery for a VEGF inhibitor, bevacizumab, has shown in preclinical studies to reduce tumor burden in rats at 1/10th the dose of injected bevacizumab, when combined with chemotherapy. To enable the next generation of inhaled monoclonal antibody (mAb) therapies by spray drying, mAb structural integrity is key. Spray dried materials undergo thermal and shear stresses, which can damage delicate mAbs. Herein we identified a set of analytical tests to evaluate the upper limits of heat and shear mAbs can withstand during spray drying. We exposed five cancer-relevant, FDA-approved mAbs to varying heat and shear stress then characterized changes to primary (1°), secondary (2°), and tertiary (3°) structure and binding activity indicative of degradation. Using the following analytical techniques we detected graduations of degradation: capillary electrophoresis-isoelectric focusing (1°), Fourier transform infrared spectroscopy (2°), Raman spectroscopy (2°), size exclusion chromatography (3°), absorbance and fluorescence spectroscopy (3°), dynamic light scattering (3°), multi-cell differential scanning calorimetry (3°), SDS-PAGE (3°), and binding activity ELISAs. Using these techniques, we developed a materials-sparing protocol to first assess whether an antibody is a candidate for spray drying, and second, to identify ideal process conditions for mAb spraying drying success. This approach will help to accelerate the development of inhaled protein therapies for lung cancer and other lung diseases. Citation Format: Madeleine Landry, Amanda Pluntze, Kimberly Shepard. Local treatment of lung cancer by inhaled monoclonal antibodies: A pre-feasibility screening approach for spray drying [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1736.