Donkor Michael, Choe Jamie, Reid Danielle Marie, Quinn Byron, Pulse Mark, Ranjan Amalendu, Chaudhary Pankaj, Jones Harlan P
Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, TX 76107, USA.
Department of Biology, Langston University, Langston, OK 73050, USA.
Pharmaceutics. 2023 Jan 29;15(2):445. doi: 10.3390/pharmaceutics15020445.
Lung metastasis is a leading cause of cancer-related deaths. Here, we show that intranasal delivery of our engineered CpG-coated tumor antigen (Tag)-encapsulated nanoparticles (NPs)-nasal nano-vaccine-significantly reduced lung colonization by intravenous challenge of an extra-pulmonary tumor. Protection against tumor-cell lung colonization was linked to the induction of localized mucosal-associated effector and resident memory T cells as well as increased bronchiolar alveolar lavage-fluid IgA and serum IgG antibody responses. The nasal nano-vaccine-induced T-cell-mediated antitumor mucosal immune response was shown to increase tumor-specific production of IFN-γ and granzyme B by lung-derived CD8 T cells. These findings demonstrate that our engineered nasal nano-vaccine has the potential to be used as a prophylactic approach prior to the seeding of tumors in the lungs, and thereby prevent overt lung metastases from existing extra pulmonary tumors.
肺转移是癌症相关死亡的主要原因。在此，我们表明，经鼻递送我们设计的包裹有CpG包被的肿瘤抗原（标签）的纳米颗粒（NPs）——鼻内纳米疫苗——通过静脉注射肺外肿瘤可显著减少肺部定植。对肿瘤细胞肺部定植的保护作用与局部黏膜相关效应和驻留记忆T细胞的诱导以及支气管肺泡灌洗液IgA和血清IgG抗体反应的增加有关。鼻内纳米疫苗诱导的T细胞介导的抗肿瘤黏膜免疫反应显示可增加肺源性CD8 T细胞对IFN-γ和颗粒酶B的肿瘤特异性产生。这些发现表明，我们设计的鼻内纳米疫苗有潜力在肺部肿瘤播种前用作预防性方法，从而预防现有肺外肿瘤的明显肺转移。
