Quantitative Cell-Based Bioassays for Individual and Combination Immune Checkpoint Immunotherapy Targets
Poster Jan 19, 2017
Zhi-jie Jey Cheng, Jamison Grailer, Pete Stecha, Jun Wang, Jim Hartnett, Frank Fan, and Mei Cong
The human immune system is comprised of a complex network of immune checkpoint receptors that are promising new immunotherapy targets for the treatment of a variety of diseases including cancer and autoimmune-mediated disorders.
Current methods used to measure the activity of antibody and other biologics drugs designed to target immune checkpoint receptors rely on primary human cells and measurement of functional endpoints such as cell proliferation, cell surface marker expression, and cytokine production. These assays are laborious and highly variable due to their reliance on donor primary cells, complex assay protocols, and unqualified assay reagents. As a result, these assays are difficult to establish in quality-controlled drug development settings.
To overcome these challenges, we developed a suite of cell-based bioluminescent reporter bioassays for individual and combination immune checkpoint immunotherapy targets including:
• PD-1 (PD-L1 or PD-L2), CTLA-4, LAG-3, TIGIT, PD-1+TIGIT
• GITR, 4-1BB, CD40, OX40
These mechanism of action (MOA)-based bioassays are available in “thaw-and-use” format and demonstrate high specificity, sensitivity, and reproducibility. The bioassays are qualified according to ICH guidelines and demonstrate the performance required for use in antibody screening, potency testing, and stability studies.
Characterization of a Type 2 diabetes-associated islet-specific enhancer cluster in STARD10 by genome editing of EndoC-βH1 cellsPoster
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
Mass Spectrometry: From Imaging to Metabolic NetworksPoster
We show that network analysis of co-localized ions from mass spectrometry imaging data provides a detailed chemo-spatial insight into the metabolic heterogeneity of tumors. Furthermore, module preservation analysis between colorectal cancer patients with and without metastatic recurrence suggests hypotheses on the nature of the different local metabolic pathways.READ MORE
Treatment Options for Chronic Parvovirus Viremia in Pediatric Heart Transplant Patients in a Tertiary Care CenterPoster
This abstract discusses three cases of pediatric heart transplant patients who suffered from parvovirus (B19) infection. Of these patients, two ( B & C) responded well to standard intravenous Ig therapy. Patient A however, did not respond to standard treatment and was begun on subcutaneous Ig, which effectively diminished his viral load. Thus, subcutaneous Ig infusions might serve as a second line treatment for transplant patients with parvovirus who do not respond well to the standard approach.READ MORE