Publicação
Optimization of strategies for anti-cancer vaccines
| Resumo: | Nowadays, cancer is one of the leading causes of death worldwide and treatments currently in use are often aggressive, invasive and not very effective. Promising therapeutic approaches include immunotherapies that has the potential to boost the immune system to fight cancer. One type of immunotherapy is provided by vaccines of dendritic cells (DCs) or containing artificial antigen presenting cells (aAPCs). These vaccines are used to expand and activate T cells against specific tumors antigens, eliminating tumor cells and providing immunological protection. Activation of T cells in vivo is lead mainly by DCs. aAPCs are artificial systems that have as main goal to mimic the function that DCs have in vivo, by presenting antigens, the first signal required for T cell activation. Vaccines of aAPCs are easier to produce and maintain and overcome the issues of patient-derived autologous DCs. The main aim of this thesis was to implement an in vitro assay to test the potential of a new generation of aAPCs, named PEMs, to activate antigen specific human T cells. PEMs consist of carbonated cores assembled with HLA-A02 molecules loaded with peptides. To verify PEMs ability to activate T cells against a specific antigen (cytomegalovirus (CMV) peptide), PEMs were co-cultured with human CD8+ T cells, isolated from healthy donors. The activation of the cells was verified by the measure of the expression of IFN-γ by qPCR and ELISA. Results showed that, in some donors, there is an increase of IFN-γ when T cells are stimulated with PEMs complexed with HLA-A02 loaded with CMV peptide, compared with negative controls. PEMs show significant binding to CD8+ T cells. With this study it was possible to conclude that PEMs are able to bind and activate T cells. However, there are still issues related to their stability and specificity. Future studies testing other aAPCs that present distinct cores and assemblies should be performed. |
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| Autores principais: | Loios, Rita Severino dos |
| Assunto: | Cancer Immunotherapies T cells APCs aAPCs |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade Nova de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório Institucional da UNL |
| Resumo: | Nowadays, cancer is one of the leading causes of death worldwide and treatments currently in use are often aggressive, invasive and not very effective. Promising therapeutic approaches include immunotherapies that has the potential to boost the immune system to fight cancer. One type of immunotherapy is provided by vaccines of dendritic cells (DCs) or containing artificial antigen presenting cells (aAPCs). These vaccines are used to expand and activate T cells against specific tumors antigens, eliminating tumor cells and providing immunological protection. Activation of T cells in vivo is lead mainly by DCs. aAPCs are artificial systems that have as main goal to mimic the function that DCs have in vivo, by presenting antigens, the first signal required for T cell activation. Vaccines of aAPCs are easier to produce and maintain and overcome the issues of patient-derived autologous DCs. The main aim of this thesis was to implement an in vitro assay to test the potential of a new generation of aAPCs, named PEMs, to activate antigen specific human T cells. PEMs consist of carbonated cores assembled with HLA-A02 molecules loaded with peptides. To verify PEMs ability to activate T cells against a specific antigen (cytomegalovirus (CMV) peptide), PEMs were co-cultured with human CD8+ T cells, isolated from healthy donors. The activation of the cells was verified by the measure of the expression of IFN-γ by qPCR and ELISA. Results showed that, in some donors, there is an increase of IFN-γ when T cells are stimulated with PEMs complexed with HLA-A02 loaded with CMV peptide, compared with negative controls. PEMs show significant binding to CD8+ T cells. With this study it was possible to conclude that PEMs are able to bind and activate T cells. However, there are still issues related to their stability and specificity. Future studies testing other aAPCs that present distinct cores and assemblies should be performed. |
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