Posters
Targeted Induction of Respiratory Immunity Provides Protection Against Secondary Lung Metastasis
Presentation Type
Poster
Discipline Track
Clinical Science
Abstract Type
Research/Clinical
Abstract
Despite medical advances in the diagnosis and treatment of cancer, metastatic cancers remain a leading cause of death in the U.S. Increasingly, novel immune-based treatments which harness the patient’s immune system has been shown to have promise for improving cancer survivorship. Such therapies take advantage of the immune system’s natural defense mechanisms to halt the formation and progression of cancer. This is mainly through the early activation of innate immune cells such as natural killer cells and the subsequent activation of the adaptive immune responses such as T and B lymphocytes which elicits a tumor-specific cytolytic and humoral antibody response, respectively. Researchers have taken advantage of these immune mechanisms of tumor defense as a complementary approach to current radio-chemo treatments, which have shown to be limited by adverse off-target effects on patients. This is particularly problematic for recurrent highly metastatic lung, brain, and bone disease, where the physiological function is a premium. Ongoing research in our laboratory is focused on developing immune-based vaccines to target local immune protection against metastatic lung disease. The expectation is that boosting immune responses at the metastatic site before seeding tumors from primary organs would mitigate metastasis and reduce mortality risks. Using an experimental murine breast cancer model of metastasis, we sought to examine the effect of intranasal vaccination to induce local and systemic adaptive immune responses as a first step in conceptualizing an immune-based vaccine. We hypothesized that an intranasal vaccine protocol would increase antigen-specific adaptive and humoral antibody responses across the respiratory tract. Our results demonstrated that intranasal vaccination provides protection against secondary lung metastasis using murine model of experimental lung metastasis. This protection was due to increased accumulation of both CD4+ and CD8+ T cells in the lungs that produced IFN- gamma as shown by flow cytometry and ELISA techniques. Again, our results show that intranasal vaccination produces higher tumor-specific IgG responses across respiratory tissues than no differences in tumor-specific IgG antibody production detected in the serum. These results provide initial findings suggesting the potential for targeted tumor vaccines to produce a local tumor-specific T-cell and antibody response with the potential to prevent tumor metastasis. Future challenge studies using spontaneous model of lung metastasis will test our working hypothesis that intranasal tumor vaccination protects the lung from tumor development in the presence of a primary breast tumor.
Recommended Citation
Donkor, Michael; Pina, Daniel; Quinn, Byron; and Jones, Harlan P., "Targeted Induction of Respiratory Immunity Provides Protection Against Secondary Lung Metastasis" (2023). Research Symposium. 121.
https://scholarworks.utrgv.edu/somrs/theme1/posters/121
Targeted Induction of Respiratory Immunity Provides Protection Against Secondary Lung Metastasis
Despite medical advances in the diagnosis and treatment of cancer, metastatic cancers remain a leading cause of death in the U.S. Increasingly, novel immune-based treatments which harness the patient’s immune system has been shown to have promise for improving cancer survivorship. Such therapies take advantage of the immune system’s natural defense mechanisms to halt the formation and progression of cancer. This is mainly through the early activation of innate immune cells such as natural killer cells and the subsequent activation of the adaptive immune responses such as T and B lymphocytes which elicits a tumor-specific cytolytic and humoral antibody response, respectively. Researchers have taken advantage of these immune mechanisms of tumor defense as a complementary approach to current radio-chemo treatments, which have shown to be limited by adverse off-target effects on patients. This is particularly problematic for recurrent highly metastatic lung, brain, and bone disease, where the physiological function is a premium. Ongoing research in our laboratory is focused on developing immune-based vaccines to target local immune protection against metastatic lung disease. The expectation is that boosting immune responses at the metastatic site before seeding tumors from primary organs would mitigate metastasis and reduce mortality risks. Using an experimental murine breast cancer model of metastasis, we sought to examine the effect of intranasal vaccination to induce local and systemic adaptive immune responses as a first step in conceptualizing an immune-based vaccine. We hypothesized that an intranasal vaccine protocol would increase antigen-specific adaptive and humoral antibody responses across the respiratory tract. Our results demonstrated that intranasal vaccination provides protection against secondary lung metastasis using murine model of experimental lung metastasis. This protection was due to increased accumulation of both CD4+ and CD8+ T cells in the lungs that produced IFN- gamma as shown by flow cytometry and ELISA techniques. Again, our results show that intranasal vaccination produces higher tumor-specific IgG responses across respiratory tissues than no differences in tumor-specific IgG antibody production detected in the serum. These results provide initial findings suggesting the potential for targeted tumor vaccines to produce a local tumor-specific T-cell and antibody response with the potential to prevent tumor metastasis. Future challenge studies using spontaneous model of lung metastasis will test our working hypothesis that intranasal tumor vaccination protects the lung from tumor development in the presence of a primary breast tumor.