Regional immune mechanisms enhance efficacy of an autologous cellular cancer vaccine with intraperitoneal administration
Widespread peritoneal dissemination is common in patients with gynecologic or gastrointestinal cancers. Accumulating evidence of a central role for regional immunity in cancer control indicates that intraperitoneal immunotherapy may have treatment advantages. This study delineates immune mechanisms...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2421029 |
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| author | Ben Marwedel Lorél Y. Medina Henning De May Joshua E. Adogla Ellie Kennedy Erica Flores Eunju Lim Sarah Adams Eric Bartee Rita E. Serda |
| author_facet | Ben Marwedel Lorél Y. Medina Henning De May Joshua E. Adogla Ellie Kennedy Erica Flores Eunju Lim Sarah Adams Eric Bartee Rita E. Serda |
| author_sort | Ben Marwedel |
| collection | DOAJ |
| description | Widespread peritoneal dissemination is common in patients with gynecologic or gastrointestinal cancers. Accumulating evidence of a central role for regional immunity in cancer control indicates that intraperitoneal immunotherapy may have treatment advantages. This study delineates immune mechanisms engaged by intraperitoneal delivery of a cell-based vaccine comprised of silicified ovarian cancer cells associated with enhanced survival. Vaccine trafficking from the site of injection to milky spots and other fat-associated lymphoid clusters was studied in syngeneic cancer models using bioluminescent and fluorescent imaging, microscopy, and flow cytometry. Spectral flow cytometry was used to phenotype peritoneal immune cell populations, while bioluminescent imaging of cancer was used to study myeloid and T cell dependency, systemic immunity, and vaccine efficacy in models of disseminated high-grade serous ovarian and DNA mismatch-repair proficient microsatellite-stable colorectal cancer. Following intraperitoneal vaccination of mice with ovarian cancer, vaccine cells were rapidly internalized by myeloid cells, with subsequent trafficking to fat-associated lymphoid clusters. Tumor clearance was confirmed to be T cell-mediated, leading to the establishment of local and systemic immunity. Combination immune checkpoint inhibitor and vaccine therapy in mice with advanced disease, characterized by an established suppressive tumor microenvironment, increased the number of mice with non-detectable tumors, however, change in tumor burden compared to vaccine monotherapy was not significant. Vaccination also resulted in tumor clearance in mouse models of metastatic colorectal cancer. This study demonstrates that intraperitoneal vaccine delivery has the potential to enhance vaccine efficacy by activating resident immune cells with the subsequent establishment of protective systemic anti-tumor immunity. |
| format | Article |
| id | doaj-art-23fce03b37b84fb5b0d93b026ac043a8 |
| institution | Kabale University |
| issn | 2162-402X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-23fce03b37b84fb5b0d93b026ac043a82024-12-03T13:49:34ZengTaylor & Francis GroupOncoImmunology2162-402X2024-12-0113110.1080/2162402X.2024.2421029Regional immune mechanisms enhance efficacy of an autologous cellular cancer vaccine with intraperitoneal administrationBen Marwedel0Lorél Y. Medina1Henning De May2Joshua E. Adogla3Ellie Kennedy4Erica Flores5Eunju Lim6Sarah Adams7Eric Bartee8Rita E. Serda9Internal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, USAInternal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, USADepartment of Obstetrics & Gynecology, University of New Mexico Health Science Center, Albuquerque, NM, USAInternal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, USAInternal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, USAInternal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, USAInternal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, USADepartment of Obstetrics & Gynecology, University of New Mexico Health Science Center, Albuquerque, NM, USAInternal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, USAInternal Medicine, University of New Mexico Health Science Center, Albuquerque, NM, USAWidespread peritoneal dissemination is common in patients with gynecologic or gastrointestinal cancers. Accumulating evidence of a central role for regional immunity in cancer control indicates that intraperitoneal immunotherapy may have treatment advantages. This study delineates immune mechanisms engaged by intraperitoneal delivery of a cell-based vaccine comprised of silicified ovarian cancer cells associated with enhanced survival. Vaccine trafficking from the site of injection to milky spots and other fat-associated lymphoid clusters was studied in syngeneic cancer models using bioluminescent and fluorescent imaging, microscopy, and flow cytometry. Spectral flow cytometry was used to phenotype peritoneal immune cell populations, while bioluminescent imaging of cancer was used to study myeloid and T cell dependency, systemic immunity, and vaccine efficacy in models of disseminated high-grade serous ovarian and DNA mismatch-repair proficient microsatellite-stable colorectal cancer. Following intraperitoneal vaccination of mice with ovarian cancer, vaccine cells were rapidly internalized by myeloid cells, with subsequent trafficking to fat-associated lymphoid clusters. Tumor clearance was confirmed to be T cell-mediated, leading to the establishment of local and systemic immunity. Combination immune checkpoint inhibitor and vaccine therapy in mice with advanced disease, characterized by an established suppressive tumor microenvironment, increased the number of mice with non-detectable tumors, however, change in tumor burden compared to vaccine monotherapy was not significant. Vaccination also resulted in tumor clearance in mouse models of metastatic colorectal cancer. This study demonstrates that intraperitoneal vaccine delivery has the potential to enhance vaccine efficacy by activating resident immune cells with the subsequent establishment of protective systemic anti-tumor immunity.https://www.tandfonline.com/doi/10.1080/2162402X.2024.2421029Cell silicificationfat-associated lymphoid clustersmilky spotsToll-like receptor agonistsvaccine |
| spellingShingle | Ben Marwedel Lorél Y. Medina Henning De May Joshua E. Adogla Ellie Kennedy Erica Flores Eunju Lim Sarah Adams Eric Bartee Rita E. Serda Regional immune mechanisms enhance efficacy of an autologous cellular cancer vaccine with intraperitoneal administration OncoImmunology Cell silicification fat-associated lymphoid clusters milky spots Toll-like receptor agonists vaccine |
| title | Regional immune mechanisms enhance efficacy of an autologous cellular cancer vaccine with intraperitoneal administration |
| title_full | Regional immune mechanisms enhance efficacy of an autologous cellular cancer vaccine with intraperitoneal administration |
| title_fullStr | Regional immune mechanisms enhance efficacy of an autologous cellular cancer vaccine with intraperitoneal administration |
| title_full_unstemmed | Regional immune mechanisms enhance efficacy of an autologous cellular cancer vaccine with intraperitoneal administration |
| title_short | Regional immune mechanisms enhance efficacy of an autologous cellular cancer vaccine with intraperitoneal administration |
| title_sort | regional immune mechanisms enhance efficacy of an autologous cellular cancer vaccine with intraperitoneal administration |
| topic | Cell silicification fat-associated lymphoid clusters milky spots Toll-like receptor agonists vaccine |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2024.2421029 |
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