Nasal Tumor Vaccination Protects against Lung Tumor Development by Induction of Resident Effector and Memory Anti-Tumor Immune Responses

Abstract

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.

Surgical Primary Tumor Resection Reduces Accumulation of CD11b+ Myeloid Cells in the Lungs Augmenting the Efficacy of an Intranasal Cancer Vaccination against Secondary Lung Metastasis

“…T cells are hallmarks for mediating antitumor immune responses in opposition to tumor cells that disseminate into the lungs [ 7 , 9 , 32 ]. In support, we have previously shown that CpG-NP-Tag nasal vaccination increases the frequency and effector functions of T cells specific for Tag in the lungs [ 23 ]. Therefore, to evaluate the efficacy of CpG-NP-Tag nasal vaccination in both non-surgery- and surgery-immunized mice, we assessed the effect of CpG-NP-Tag nasal vaccination on T cell infiltration and effector functions in the lungs of vaccinated mice, including both non-surgery and surgery mice.…”

“…Capitalizing on the well-established strategies to deliver drugs to the lungs; for example, through intranasal administration, we engineered a nasal nano-vaccine: CpG-coated nanoparticles encapsulating tumor antigens (whole cell lysate) from mammary tumor cells. We previously showed that prior immunization (via intranasal instillation of nano-vaccine) prevented lung colonization through mammary tumor cells after intravenous injection [ 23 ]. In support, one study has shown that prior intranasal immunization with a melanoma cancer vaccine prevented lung colonization through melanoma cells after a challenge using a tail vein injection [ 31 ].…”

“…Buprenorphine (0.005 mg/kg; sc) was administered promptly after surgery and again 12 h later for pain management. Lung leukocytes and BALF cells isolated as previously described [23] were stained for 1hr at 4 • C with anti-mouse CD45 APC (clone; 30-F11, Tonbo Biosciences, San Diego CA, USA), anti-mouse CD3 FITC (clone; 17A2, Tonbo Biosciences, San Diego, CA, USA), anti-mouse CD4 BV605 (clone; GK 1.5, Biolegend, San Diego, CA, USA), anti-mouse CD8 PE (clone; 2.43, Tonbo Biosciences, San Diego, CA, USA) and anti-mouse PD-1 PE-Cy5 (clone; 29F.1A12, Biolegend, San Diego, CA, USA).…”

“…Over the years, cancer vaccines have been used to induce antitumor immunity within the tumor microenvironment by stimulating endogenous T cells to attack tumor cells [ 20 , 21 , 22 ]. Accordingly, we have recently engineered an intranasal cancer vaccine (CpG-NP-Tag), utilizing targeted nano-vaccine delivery to pre-empt secondary lung metastasis by priming and boosting antitumor immunity in the lung [ 23 ]. We showed that our nasal nano-vaccine-induced localized mucosal-associated effector T cells and antibody immune responses were associated with a significant reduction in lung colonization by 4T1 cells, which are highly carcinogenic with high proclivity to metastasize to the lung in female BALB/c mice.…”

Pulmonary delivery of nano‐particles for lung cancer diagnosis and therapy: Recent advances and future prospects

“…Donkor et al developed a nano-vaccine for nasal airway delivery to prevent the formation of lung metastases caused by primary tumors. They synthesized a CpG-NP-Tag nano-vaccine encapsulating a tumor antigen and demonstrated its ability to prevent lung metastasis in a 4T1 triple-negative breast cancer model, suggesting the respiratory tract delivery of nano-vaccine CpG-NP-Tag may be used as a preventive method for lung metastasis of primary tumors (Donkor et al, 2023). These studies provide new evidence for lung cancer treatment by nanomaterials as antigenic vaccines delivered through the respiratory tract, providing a new therapeutic opportunity to prevent and treat lung cancer.…”