Multiplexing Phenotype and Function for More Biologically Relevant Insights - 34

Related Article from
small molecule moiety and also the antibody," elaborated Dr. Chung. "When a small
molecule (toxin) is conjugated to a large molecule, like a protein, then that toxin
itself can be immunogenic." Furthermore, the assay should demonstrate which step
in a multistep mechanism of action the antibody exerts its neutralizing effect.

immune system, it blocks the activity of a T-cell receptor that induces luminescence.
However, adding an immunotherapy that disrupts the PD-1/PD-L1 interaction to the
assay re-establishes T-cell receptor activity and generates a measurable luminescence signal that allows assessment of drug effectiveness and potency.

Dr. Chung cited drug interference as the second most significant challenge in NAb
assay development. "Patients receive high doses of the drug, so these samples
contain not only ADAs, but also a high drug concentration that can interfere with
the assay," he explained. Referred to as the "drug tolerance" of the assay, the ability
to obtain reliable results from drug-containing samples is a common theme for
NAb studies, and different methods to remove excess drug and purify patient ADAs,
including acid dissociation and affinity extraction, have emerged as possible solutions.

"The main challenge in building a reporter gene bioassay is identifying the most
biologically relevant cell background and signaling pathway to accurately model a
drug's potency and mechanism of action," stated Dr. Somberg.

Checking Checkpoint Targeting
Immuno-oncology has become a very active area of drug development for many
biopharmaceutical companies, and a prominent therapeutic strategy is combination immunotherapy. "Our customers are looking at the exhausted T-cell phenotype
and understanding that there may be multiple inhibitory receptors present, and
if you target multiple receptors, such as PD-1 and CTLA-4, you see a much more
pronounced effect," commented Richard Somberg, Ph.D., strategic collaborations
manager, Promega.
Promega has developed portfolios featuring functional cell-based assays for both
co-inhibitory and co-stimulatory immune checkpoint targets. To assess the response
of co-inhibitory receptors, Promega has developed a dual-cell platform that represents the immune system with a Jurkat human T-cell line and an antigen-expressing
cell with an easy-to-culture cell line-typically CHO cells. The platform mimics a
drug's mechanism of action in a simple system that lets researchers interrogate
activation pathways using a luciferase reporter construct.
For example, Promega has modeled the interaction between PD-1 (programmed
cell death protein 1) and PD-L1 (programmed cell death ligand 1). The result is the
company's PD-1/PD-L1 Blockade Bioassay. It contains a co-culture of genetically
engineered Jurkat and CHO cell lines expressing PD-1 and PD-L1, respectively.
When PD-1 engages PD-L1, activating a mechanism used by tumors to evade the
34

| January, 2019

Designing a cell-based assay requires a solid understanding of the underlying drug
mechanism of action, and the variety of methods used to simplify and model these
mechanisms are as varied as the mechanisms themselves. The Immunogenicity
BioAssay Summit provided a lens into the vast array of assays that can help ensure
the safety and efficacy of new drugs.
"For one of the first times, it's not 'you have one more month to live'," reflected Dr.
Somberg on the clinical success of both mono- and combination therapies. "They're
actually seeing prolonged response rates, and that's really encouraging." n


http://www.genengnews.com

Multiplexing Phenotype and Function for More Biologically Relevant Insights

Table of Contents for the Digital Edition of Multiplexing Phenotype and Function for More Biologically Relevant Insights

Contents
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 1
Multiplexing Phenotype and Function for More Biologically Relevant Insights - Contents
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 3
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 4
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 5
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 6
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 7
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 8
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 9
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 10
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 11
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 12
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 13
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 14
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 15
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 16
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 17
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 18
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 19
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 20
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 21
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 22
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 23
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 24
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 25
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 26
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 27
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 28
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 29
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 30
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 31
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 32
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 33
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 34
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 35
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 36
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 37
Multiplexing Phenotype and Function for More Biologically Relevant Insights - 38
https://www.nxtbookmedia.com