Dual antigen transfer pathways mediate highly efficacious anti-tumor immunity induced by intravenously injected antigen-loaded monocytes
| Autor: | Min-Nung Huang, Lowell Nicholson, Kristen Batich, David Kopin, Vijay Prabhakar, Barbara Lipes, John Sampson, Michael Gunn |
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| Rok vydání: | 2017 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 198:79.21-79.21 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Dendritic cells (DC) have been key elements in developing effective cancer vaccines to induce potent anti-tumor immunity. However, the common approach adopted in clinical trials using ex vivo generated DC loaded with tumor antigens (Ag) has been challenged by its limited clinical response, complexity, and quality of the manufacturing process. Alternative efforts focused on in vivo Ag loading on endogenous DCs have not yet been well validated in their efficacy for cancer treatment, suggesting the efficiency of in vivo Ag transfer from Ag-carrying vehicles to DCs needs to be further improved. As an attempt to bypass the aforementioned problems, we are testing the hypothesis that Ag-loaded monocytes can induce efficacious anti-tumor T cell responses by directly presenting Ag to T cells through in vivo monocyte-to-DC differentiation. We find that intravenously (IV) injected monocytes loaded with either model or known tumor Ag induce robust Ag-specific CD4 and CD8 T cell responses in mice without triggering antibody responses, display anti-tumor efficacy superior to that seen with traditional adjuvants or RNA-pulsed DC vaccines, and can be combined with checkpoint blockade to increase their efficacy. Unexpectedly, monocyte-induced T cell responses do not require Ag presentation by monocytes themselves, but rather the transfer of Ag to endogenous splenic DC. This transfer occurs via gap junctions for CD8 T cell responses and via macrophages for CD4 T cell responses. These findings demonstrate the existence of efficient dual Ag transfer pathways between monocytes and splenic DCs and suggest that the administration of Ag-loaded monocytes may serve as a simple and efficacious immunotherapeutic platform for the treatment of human cancers. |
| Databáze: | OpenAIRE |
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