Quantitative Cell-Based Bioassays for Individual or Combination Immune Checkpoint Immunotherapy
Poster Dec 07, 2017
Jamison Grailer, Pete Stecha, Julia Gilden, Denise Garvin, Jim Hartnett, Frank Fan, Mei Cong and Zhi-jie Jey Cheng
Immunotherapy aims to boost a patient’s own immune system to fight disease. Activation of T cells via direct stimulation of the T cell receptor or by modulating immune checkpoint pathways are two strategies being employed individually and in combination. Immune checkpoint targets include co-inhibitory (e.g. PD-1, CTLA-4, TIGIT, LAG-3) and co-stimulatory (e.g. GITR, 4-1BB, OX40, CD40) receptors.
Genome-wide association studies (GWAS) have identified more than 100 genetic loci associated with type 2 diabetes. The majority of these are located in the intergenic or intragenic regions suggesting that the implicated variants may alter chromatin conformation. This, in turn, is likely to influence the expression of nearby or more remotely located genes to alter beta cell function. At present, however, detailed molecular and functional analyses are still lacking for most of these variants. We recently analysed one of these loci and mapped five causal variants in an islet-specific enhancer cluster within the STARD10 gene locus. Here, we aimed to understand how these causal variants influence b-cell function by alteration of the chromatin structure of enhancer clusterREAD MORE