- This topic has 39 replies, 6 voices, and was last updated 10 years, 10 months ago by
.
-
-
-
-
-
-
-
-
-
-
-
-
Your question about timing is a very good one. My theory is based on activation of the T-cells (CD-4 and CD8). CD-4 is the helper T-cell and CD-8 is known as the cytotoxic T-cell. These T-cells grow and propagate at different growth patterns. In the literature, CD4 cells growth in vivo takes about 33 days. Where as the CD-8 T-cells take about 49 days to reach its maximum propagation. Now the amount of time may differ from patient to patient base on microenvironment of the cells. This means there can be a lot of different cytokines present or made by these cells that can hinder, delay or help propagate these cells.
Also, once the T-cells are activated, within 3 -6 days the receptors CTLA-4, PD-1 and others upregulate from within the and surface to the outer layer of the T-cells. These receptors will then bind to other proteins that complete the signaling to shut down the T-cell activation. This our body’s way of making sure our T-cells don’t over react to the immune response. That is why the anti-bodies of the receptors (yervoy and Anti-PD-1) are called checkpoint modulators.
Now to get back to the timing. IL-2, Think of it as growth factor/fertilizer for your cells. If IL-2 is dosed to early in the growth process, the suppressive Tregs will grow faster than the CD4 helper T-cells and can shut down the immune response.
If IL-2 is added late in growth (50 days or longer) it has been shown that CD-8 T-cells (Cytotoxic T-cells) seem to flourish. When supplied exogenously, IL-2 increases the magnitude of cytolytic activity generated. (Baker et al., 1978)
L-2 therapy was highly beneficial during the death phase, resulting in increased proliferation and survival of Tumor-specific T cells. IL-2 treatment also increased proliferation of resting memory T cells in the host that controlled the disease. Tumor-specific T cells in chronically infected Host also responds to IL-2 resulting in decreased tumor burden. Thus, timing of IL-2 administration and differentiation status of the T cell are critical parameters in designing IL-2 therapies (Blattman et al., 2003).
-
Your question about timing is a very good one. My theory is based on activation of the T-cells (CD-4 and CD8). CD-4 is the helper T-cell and CD-8 is known as the cytotoxic T-cell. These T-cells grow and propagate at different growth patterns. In the literature, CD4 cells growth in vivo takes about 33 days. Where as the CD-8 T-cells take about 49 days to reach its maximum propagation. Now the amount of time may differ from patient to patient base on microenvironment of the cells. This means there can be a lot of different cytokines present or made by these cells that can hinder, delay or help propagate these cells.
Also, once the T-cells are activated, within 3 -6 days the receptors CTLA-4, PD-1 and others upregulate from within the and surface to the outer layer of the T-cells. These receptors will then bind to other proteins that complete the signaling to shut down the T-cell activation. This our body’s way of making sure our T-cells don’t over react to the immune response. That is why the anti-bodies of the receptors (yervoy and Anti-PD-1) are called checkpoint modulators.
Now to get back to the timing. IL-2, Think of it as growth factor/fertilizer for your cells. If IL-2 is dosed to early in the growth process, the suppressive Tregs will grow faster than the CD4 helper T-cells and can shut down the immune response.
If IL-2 is added late in growth (50 days or longer) it has been shown that CD-8 T-cells (Cytotoxic T-cells) seem to flourish. When supplied exogenously, IL-2 increases the magnitude of cytolytic activity generated. (Baker et al., 1978)
L-2 therapy was highly beneficial during the death phase, resulting in increased proliferation and survival of Tumor-specific T cells. IL-2 treatment also increased proliferation of resting memory T cells in the host that controlled the disease. Tumor-specific T cells in chronically infected Host also responds to IL-2 resulting in decreased tumor burden. Thus, timing of IL-2 administration and differentiation status of the T cell are critical parameters in designing IL-2 therapies (Blattman et al., 2003).
-
Your question about timing is a very good one. My theory is based on activation of the T-cells (CD-4 and CD8). CD-4 is the helper T-cell and CD-8 is known as the cytotoxic T-cell. These T-cells grow and propagate at different growth patterns. In the literature, CD4 cells growth in vivo takes about 33 days. Where as the CD-8 T-cells take about 49 days to reach its maximum propagation. Now the amount of time may differ from patient to patient base on microenvironment of the cells. This means there can be a lot of different cytokines present or made by these cells that can hinder, delay or help propagate these cells.
Also, once the T-cells are activated, within 3 -6 days the receptors CTLA-4, PD-1 and others upregulate from within the and surface to the outer layer of the T-cells. These receptors will then bind to other proteins that complete the signaling to shut down the T-cell activation. This our body’s way of making sure our T-cells don’t over react to the immune response. That is why the anti-bodies of the receptors (yervoy and Anti-PD-1) are called checkpoint modulators.
Now to get back to the timing. IL-2, Think of it as growth factor/fertilizer for your cells. If IL-2 is dosed to early in the growth process, the suppressive Tregs will grow faster than the CD4 helper T-cells and can shut down the immune response.
If IL-2 is added late in growth (50 days or longer) it has been shown that CD-8 T-cells (Cytotoxic T-cells) seem to flourish. When supplied exogenously, IL-2 increases the magnitude of cytolytic activity generated. (Baker et al., 1978)
L-2 therapy was highly beneficial during the death phase, resulting in increased proliferation and survival of Tumor-specific T cells. IL-2 treatment also increased proliferation of resting memory T cells in the host that controlled the disease. Tumor-specific T cells in chronically infected Host also responds to IL-2 resulting in decreased tumor burden. Thus, timing of IL-2 administration and differentiation status of the T cell are critical parameters in designing IL-2 therapies (Blattman et al., 2003).
-
Publications or clinical trials investigating the timing for combining checkpoint inhibitors with IL-2 administration are very scarce due to the fact that Big Pharma wants to use their drugs as a mono-therapy. It is a lot easier to get FDA approval mono-therapy than a combinatorial therapy. So the big Pharma will do clinical trials as a mono-therapy and then maybe as a combinatorial therapy. Only time will tell.
-
Publications or clinical trials investigating the timing for combining checkpoint inhibitors with IL-2 administration are very scarce due to the fact that Big Pharma wants to use their drugs as a mono-therapy. It is a lot easier to get FDA approval mono-therapy than a combinatorial therapy. So the big Pharma will do clinical trials as a mono-therapy and then maybe as a combinatorial therapy. Only time will tell.
-
-
-
-
-
-
-
-
-
-
-
-
-
Publications or clinical trials investigating the timing for combining checkpoint inhibitors with IL-2 administration are very scarce due to the fact that Big Pharma wants to use their drugs as a mono-therapy. It is a lot easier to get FDA approval mono-therapy than a combinatorial therapy. So the big Pharma will do clinical trials as a mono-therapy and then maybe as a combinatorial therapy. Only time will tell.
-
-
-
-
-
- You must be logged in to reply to this topic.