CD90-Targeted Liposomes Increase the Therapeutic Efficacy of a Retinoic Acid Derivative in Pulmonary Carcinoma

Abstract

Title: The therapeutic efficacy of CD90-targeted liposomes in pulmonary carcinoma. Background: In refractory lung cancer tissue, it has been reported that cell populations exist that exhibit resistance to existing therapeutics. These cells have characteristics such as high stemness and tumorigenic potential, and they are thought to contribute to relapse and metastasis. Differentiation inducer 4[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl) carbamoyl] benzoic acid (Am80) has a growth inhibitory effect on pulmonary carcinoma cells, but it has been effective only in a high dose that causes damage to normal cells. We aimed to achieve a dose reduction by specific targeting of anaplastic pulmonary carcinoma cells and modification of antibodies on the liposome surface specific for membrane protein of undifferentiated cells because undifferentiated pulmonary cells have unique membrane proteins. CD90 is one of the undifferentiated markers expressed in pulmonary cells. Methods and Findings: In this study, we examined the usefulness evaluation of Am80 liposomes conjugated with anti-CD90 antibody using Calu-6, a CD90-positive undifferentiated human pulmonary carcinoma cell line. After the preparation of Am80 liposomes, the characterization and cell specificity, therapeutic efficacy of them were assessed. Am80 liposomes conjugated with antibody selectively combined with the surface of Calu-6 and had a significant influence on the inhibition of cell and tumor growth. The twice-weekly intratumoral administration of Am80 liposomes conjugated antibody (0.1 mg/kg as Am80) inhibited tumor growth to 3.64 ± 1.10 compared to empty liposomes (5.89 ± 1.61) in relative tumor volume at day 28. Conclusions: We revealed that the cellular uptake of Am80 liposomes conjugated with anti- CD90 antibody by anaplastic pulmonary carcinoma cells was highly effective and efficient.