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group_3_presentation_2_-_oncolytic_immunotherapy [2016/03/11 23:04] domazee |
group_3_presentation_2_-_oncolytic_immunotherapy [2018/01/25 15:19] (current) |
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| The mechanisms of oncolytic immunotherapy can be broken down into two major effects: the local effects and the systemic effects.<sup>1</sup> The local effects consist of tumour cell lysis.<sup>1</sup> The oncolytic virus (OV) must first selectively target cancer cells and replicate.<sup>1</sup> Next, the tumour cells lyse, thus representing the oncolytic effect.<sup> 1 </sup> Furthermore, the systemic effects include the tumour-specific immune response, which activates antigen presenting immune cells.<sup> 1 </sup> This primes the adaptive immune response and leads to a series of downstream effects that result in death of distant cancerous cells.<sup>2</sup> | The mechanisms of oncolytic immunotherapy can be broken down into two major effects: the local effects and the systemic effects.<sup>1</sup> The local effects consist of tumour cell lysis.<sup>1</sup> The oncolytic virus (OV) must first selectively target cancer cells and replicate.<sup>1</sup> Next, the tumour cells lyse, thus representing the oncolytic effect.<sup> 1 </sup> Furthermore, the systemic effects include the tumour-specific immune response, which activates antigen presenting immune cells.<sup> 1 </sup> This primes the adaptive immune response and leads to a series of downstream effects that result in death of distant cancerous cells.<sup>2</sup> | ||
| - | <box 45% round | > {{:screen_shot_2016-03-10_at_4.12.12_pm.png?550|}} </box| Figure 1 - Summary of local and systemic effects of T-VEC in healthy vs. tumour cells (Andtbacka et al., 2015). > | + | <box 55% round | > {{:screen_shot_2016-03-10_at_4.12.12_pm.png?550|}} </box| Figure 1 - Summary of local and systemic effects of T-VEC in healthy vs. tumour cells (Andtbacka et al., 2015). > |
| ===== Oncolytic Immunotherapy ===== | ===== Oncolytic Immunotherapy ===== | ||
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| - | <box 46% round right | >{{:screen_shot_2016-03-11_at_2.00.21_pm.png?450|}} </box| Figure 2 - Treatment with oncolytic immunotherapy at baseline (left) and at 6 months (right) (IMWJ, 2010).> | + | <box 40% round right | >{{:screen_shot_2016-03-11_at_2.00.21_pm.png?400|}} </box| Figure 2 - Treatment with oncolytic immunotherapy at baseline (left) and at 6 months (right) (IMWJ, 2010).> |
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| The activation of cytotoxic CD8 cells occurs through two methods. The first method of activation of CD8 cells occurs in a very similar manner to the CD4 cells. In this case, the CD8 cell co-receptor binds to the peptide:MHC Class I complex.<sup>13</sup> The binding of the B7 co-stimulatory ligand to the CD28 co-stimulatory receptor is required for CD8 cell activation as well.<sup>13</sup> When CD8 cells are activated by these intracellular interaction, they synthesize interleukin (IL) -2, which is a cytokine, and the IL-2 receptor.<sup>13</sup> This subsequent interaction allows for proliferation and differentiation of CD8 cells.<sup>13</sup> If this process does not provide sufficient co-stimulation, the CD4 effector cells can help to activate naïve virus-specific CD8 cells as well.<sup>13</sup> In this case, the DC interacts with both CD4 and CD8 T-cells through interactions with the peptide:MHC Class II complex and the peptide:MHC Class I complex, respectively.<sup>13</sup> In addition, the IL-2 cytokine that is secreted by the CD4 cell binds to the IL-2 receptor on the CD8 cell, which leads to proliferation and differentiation of the CD8 cell.<sup>13</sup> The activated cytotoxic CD8 cells can now exit the lymph nodes and travel throughout the body to kill distant tumour cells. | The activation of cytotoxic CD8 cells occurs through two methods. The first method of activation of CD8 cells occurs in a very similar manner to the CD4 cells. In this case, the CD8 cell co-receptor binds to the peptide:MHC Class I complex.<sup>13</sup> The binding of the B7 co-stimulatory ligand to the CD28 co-stimulatory receptor is required for CD8 cell activation as well.<sup>13</sup> When CD8 cells are activated by these intracellular interaction, they synthesize interleukin (IL) -2, which is a cytokine, and the IL-2 receptor.<sup>13</sup> This subsequent interaction allows for proliferation and differentiation of CD8 cells.<sup>13</sup> If this process does not provide sufficient co-stimulation, the CD4 effector cells can help to activate naïve virus-specific CD8 cells as well.<sup>13</sup> In this case, the DC interacts with both CD4 and CD8 T-cells through interactions with the peptide:MHC Class II complex and the peptide:MHC Class I complex, respectively.<sup>13</sup> In addition, the IL-2 cytokine that is secreted by the CD4 cell binds to the IL-2 receptor on the CD8 cell, which leads to proliferation and differentiation of the CD8 cell.<sup>13</sup> The activated cytotoxic CD8 cells can now exit the lymph nodes and travel throughout the body to kill distant tumour cells. | ||
| - | <box 42% round centre | >{{:picture1.png?400|}} </box| Figure 8 - CD4 T cells can assist with the activation of CD8 T cells through the interaction of IL-2 on the CD8 T cell (Parham, 2015). > | + | <box 31% round centre | >{{:picture1.png?300|}} </box| Figure 8 - CD4 T cells can assist with the activation of CD8 T cells through the interaction of IL-2 on the CD8 T cell (Parham, 2015). > |
| === Cytotoxicity of CD8 Cells=== | === Cytotoxicity of CD8 Cells=== | ||
