This is totally cool and also a good review of many of the mechanisms we learned this semester. This group in Texas is making an effort to more effectively eliminate tumor cells in patients with malignant non-Hodgkin's lymphomas (NHL) of B-cell lineages by priming (ie adding an adjuvant) to a DNA vaccination. The working model being- that relapse following an initial anti-tumor treatment is due to inadequate removal of tumor cells. They’ve engineered microparticles loaded with chemokines, tumor specific DNA antigen, and an IL-10 silencing mechanism (siRNA).
Immature DCs are recruited via the chemokines, take in the microparticles by endocytosis, and travel to lymph nodes presenting the tumor specific DNA antigen in MHCII on their surface. This elicits a T cell response and, because of the siRNA, gene expression of IL-10 in the DCs is silenced at the post-transcriptional level. This shifts the immune response towards a Th1 response. Remember, IL-10 from DCs would normally act to inhibit a Th1 response and encourage a Th2 response.
An increased Th1 response means more CD8+ CTLs are activated in the lymph nodes following DC contact and with help from CD4+ Th1s releasing IL-2. There is clonal expansion and the activated, tumor cell-specific CTLs then travel to the site of antigen recognition where they do a couple of things. 1. They administer the “kiss of death” to the lymphoma cells exhibiting the antigen for which they are specific and, 2. they release IFNgamma, upon engagement of the TCR with the lymphoma cell. IFNgamma is pro-inflammatory and leads to activation of macrophages (M0) into classically activated “angry” M1s.
This study found a significantly increased CD8+ cytotoxic T cell (CTL) response and stronger CD4+ CTL activity when compared to the DNA vaccine alone.
Source:
An injectable synthetic immune-priming center mediates efficient T-cell class switching and T-helper 1 response against B cell lymphoma.
Journal of Controlled Release, Volume 155, Issue 2, 30 October 2011, Pages 184-192
Ankur Singh, Hong Qin, Irina Fernandez, Jinsong Wei, Jian Lin, Larry W. Kwak, Krishnendu Roy
Hello,
ReplyDeleteYou have provided a very good site to knowing about cytotoxic T cell. These cells recognize their targets by binding to antigen associated with MHC class I, which is present on the surface of nearly every cell of the body. They call the cytotoxic T cells and suppressor T cells to help...