When You Fight Disease with a One-Two Punch

Imagine attacking diseases like cancer or rheumatoid arthritis in two different ways with one single medicine; that’s what research on bispecifics is trying to achieve.  

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The progression of complex diseases like cancer, immune-mediated and neurological conditions often involves multiple disease pathways. Medicines that attack one target can bring benefits to patients, but researchers see room to advance the science even further. Enter bispecifics.
 
“A ‘bispecific’ is a biological therapy that binds to two different targets with the goal of enhanced effectiveness in treating diseased tissues,” says Susan Morgan-Lappe, Ph.D., associate director, oncology discovery, AbbVie. “With bispecifics, we are researching how we can deliver a one-two punch against the disease.”
 
How can bispecifics be created? One way is through a technology platform with a complicated name: Dual-Variable Domain Immunoglobulin (DVD-Ig) proteins. DVD-Ig allows two antibodies that target different disease pathways to be combined into a single medicine that blocks the functioning of two distinct targets.  

Combing two mechanisms for a unique outcome

As we better understand the complexities of human disease, bispecifics are increasing in sophistication.
 
“We’re discovering new biology,” says Tariq Ghayur, Ph.D., distinguished research fellow at the AbbVie Bioresearch Center in Worcester, Massachusetts, U.S.A. “By combining two different mechanisms into one molecule, we want to accomplish a unique outcome that can’t be achieved with the two molecules separately.”
 
An example of this is a bispecific that may allow for a more site-directed or disease-specific targeting.
 
“We are exploring the design of the outer domain of the molecule – the part of the molecule that seeks out the target – so it only finds a very specific protein (antigen) that is found on a particular diseased tissue and not on healthy cells,” Morgan-Lappe says. “Once at the target, the inner domain can also do its job to treat the diseased tissue.”
 
Bispecifics also have an important role to play in immuno-oncology, where scientists are developing therapies that will reactivate the body’s own immune system to attack and kill cancer cells.
 
Instead of blocking the function of two targets – as is the case for immune-mediated diseases – in immuno-oncology scientists are using a bispecific to build a bridge, connecting cancer-killing T cells to the specific target on the tumor.

article_image_bispecifics_ribbon1.jpg
An x-ray structure of DVD-Ig in ribbon diagram

Going a step further

And there’s more; combining three antibodies is possible.  

“What we have done now is to take the DVD-Ig backbone and add a third antibody to create the next generation of highly differentiated molecules,” Ghayur says. “These molecules will target three distinct disease pathways, or will better modulate cancer-fighting capabilities of the body’s immune system, which we hope will improve efficacy in future therapies.”
 
Researching different types of bispecifics allows for flexibility in the drug discovery and development process and is an important part of the discovery toolbox across immune-mediated diseases and cancer.
 
When scientists select their targets and determine the end goal, the right tool can be selected for the job and hopefully result in new therapies that will make a real difference for patients.
 
AbbVie is currently investigating four DVD-Igs in various phases of clinical development in both immunology and oncology.

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Jaquelin Finley
Email: jaquelin.finley@abbvie.com
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