Nanomedicine-Based Gene Delivery for a Truncated Tumor Suppressor RB94 Promotes Lung Cancer Immunity

Abstract

Because lung cancer remains the most common and lethal of cancers, novel therapeutic approaches are urgently needed. RB94 is a truncated form of retinoblastoma tumor suppressor protein with elevated anti-tumor efficacy. Our investigational nanomedicine (termed scL-RB94) is a tumor-targeted liposomal formulation of a plasmid containing the gene encoding RB94. In this research, we studied anti-tumor and immune modulation activities of scL-RB94 nanocomplex in preclinical models of human non-small cell lung cancer (NSCLC). Systemic treatment with scL-RB94 of mice bearing human NSCLC tumors significantly inhibited tumor growth by lowering proliferation and increasing apoptosis of tumor cells in vivo. scL-RB94 treatment also boosted anti-tumor immune responses by upregulating immune recognition molecules and recruiting innate immune cells such as natural killer (NK) cells. Antibody-mediated depletion of NK cells blunted the anti-tumor activity of scL-RB94, suggesting that NK cells were crucial for the observed anti-tumor activity in these xenograft models. Treatment with scL-RB94 also altered the polarization of tumor-associated macrophages by reducing immune-suppressive M2 macrophages to lower immune suppression in the tumor microenvironment. Collectively, our data suggest that the efficacy of scL-RB94 against NSCLC is due to an induction of tumor cell death as well as enhancement of innate anti-tumor immunity.

Codelivery of CPT and siPHB1 with GSH/ROS Dual-Responsive Hybrid Nanoparticles Based on a [12]aneN3-Derived Lipid for Synergistic Lung Cancer Therapy

“…Cancer is one of the major threats to human health, and the incidence of cancer continues to increase worldwide . Among them, lung cancer is one of the cancers with higher mortality, and most lung cancer patients are diagnosed at an advanced stage, resulting in historically poor median overall survival (OS) and no significant reduction in morbidity. − Chemotherapeutic drugs were commonly used in lung cancer treatment, but the low therapeutic index, severe treatment-associated adverse effects, and multidrug resistance developed by tumor cells hampered their clinical application. , Gene-based, such as DNA, miRNA, and siRNA, therapeutic strategies have attracted increasing attention for lung cancer treatment because of their great potential to eliminate malignant tumors. − Successful gene-based therapy depends on the effective delivery of therapeutic genes into tumor cells. Instead of virus-based vector systems, increasing efforts have been made to design nonviral gene carriers due to their high security and good immunogenicity. − …”