The last two decades saw an unprecedented
expansion in the study of human biology, with advances in human
genetics, cancer genomics, stem cell biology, bioinformatics and
systems biology all paving the way for new therapies. In the future,
advances not only in medicinal chemistry but in areas such as protein
engineering, antibody drug conjugates, bispecifics and immunotherapies
will bring new targets into reach.
Explore some of the technologies and
platforms we are using to discover and develop innovative medicines.
One way to enhance the therapeutic potential of antibodies is to
combine, or “conjugate,” them with small molecule drugs, which
enhances the antibody’s ability to target a specific antigen. Another
way to boost the therapeutic potential of antibodies is to use a
technology that allows the generation of a dual specific antibody to
target two antigens (also called a dual-variable domain [DVD] antibody).
Our bispecific platform is a technology that holds great promise. In
the past, this has been referred to as DVD platform. In fact, this
platform is capable of producing a wide range of different bispecific
formats and DVD is just a small portion. These bispecific formats have
a broad range of protein binding and biologic characteristics.
In oncology, we view our bispecific platform as a path to new
biology rather than simply to combination therapy. For example, we are
studying the uses of our bispecifics to enhance the performance of
antibody-drug conjugates (ADCs). In preclinical systems, we can show
that a bispecific that binds to two portions of the same molecular
target is taken up in the cancer cells better than a traditional ADC.
This could deliver a greater toxin load, thereby enhancing efficacy.
Similarly, a bispecific that binds to two molecular targets from the
same cancer cell can be used to increase tumor specificity, allowing
us to prosecute targets that had some degree of expression in normal
tissue. With our bispecific platform, we are able to create a wide
range of protein constructs, ultimately leading to new biology with
different mechanisms of action.
We are exploring several new methods for delivering medicines that
are more precise and impactful. From reducing the effect of
chemotherapy on healthy cells to opening new avenues for treating
neurodegenerative diseases, our research on innovative, targeted drug
delivery aims to change the way disease is treated.
ADCs represent a proven technology platform that delivers a
therapeutic agent directly to where it’s needed using precise
targeting of an antibody.
An ADC takes a highly potent toxin, one that is too potent to be
administered systemically, and couples it to a monoclonal antibody so
that it can be delivered directly to cancer cells, sparing normal
tissue. The idea behind ADCs is not new, but it is only recently that
the progress in target identification, antibody engineering, linker
chemistry and toxin technology have come together to make this a
Our strength in discovering and developing highly specific
monoclonal antibodies and our experience in small molecule chemistry
and analytics make ADCs a strong focus area of development for AbbVie.
Cancer stem cells are the roots of a tumor. They initiate and
perpetuate tumor growth and are more resistant to chemotherapy and
radiation therapies. Cancer stem cells are the tumor cells that
metastasize, causing cancer to spread throughout the body.
With work initiated by Stemcentrx, our therapies are engineered to
target cancer stem cells, subsequently delivering a potent drug that
can kill them. We believe that targeting and eliminating cancer stem
cells will enable long-term patient survival.
The complex and intricate system of cells that carries blood to the
brain and spinal cord tissue is difficult to penetrate with biologic
medicines. That’s why we are exploring new ways to cross the
blood-brain barrier with nanoparticles and protein capsules. These
innovative drug delivery systems may lead to advances in discovering
and developing new medicines to treat diseases of the brain, like
Alzheimer’s and Parkinson’s.
As we better understand human biology, we can also leverage the body
to uncover new ways to fight disease. Cancer and immune-mediated
diseases are two areas where recent research is showing how new
solutions might come from within.
In oncology, we want to turn up the immune system to attack tumors,
while for immunological diseases, we want to turn it down because it’s
doing damage by attacking normal tissue inappropriately. The key to
treating both types of diseases may involve immunotherapies.
For example, there is a constant battle between the immune system
and tumors. Tumors use various mechanisms to avoid destruction by
immune cells. One of the ways they do that is by engaging checkpoint
receptors on immune cells. Checkpoint molecules are key off switches
in immune cells and their activation blocks an immune response to
target what is identified as “foreign” in the body. When tumors engage
these checkpoints, it makes it difficult for immune cells to identify
the tumor as something they need to attack, thereby dampening their
activity. The biggest breakthrough in immunotherapy in recent years
came when scientists discovered that disrupting these checkpoint
receptors could activate immune cells and result in antitumor responses.
The antitumor activity of checkpoint inhibitors teaches us that
tumors can be controlled by the immune system, but checkpoint blockade
is only one approach. We have been looking at various approaches
beyond checkpoint inhibitors for several years.
There has been an increased emphasis on the gut microbiome in recent
years. The bacteria and microorganisms in our gastrointestinal tract
that perform critical functions like digestion and vitamin production,
and the ability to easily reprogram bacteria to perform other
functions are changing the way researchers tackle serious diseases.
Together with Synlogic, we are studying the gut microbiome to develop
new medicines for treating inflammatory bowel disease.
Our medicines are only as effective as our ability to deliver them.
We continue to look for new ways to ensure our discoveries can be
manufactured and delivered to patients safely and with the highest quality.
Success in biologics manufacturing is largely measured by product
reproducibility. Through sophisticated cell line development, cell
culture manufacturing and quality control, we overcome the complexity
of large molecule manufacturing to deliver consistent drug
performance. Our expertise in biologics is rooted in having developed
the first fully human monoclonal antibody. Today, our biologics
manufacturing team continues to be leaders in the field, providing
scientific support for all aspects of our manufacturing. Our team
partners with R&D and our contract manufacturing clients to scale
up and transfer new products into commercial manufacturing sites,
troubleshoot technical problems associated with product manufacturing
or laboratory tests and identify and implement process enhancements to
increase yields or throughput. We support chemical and fermentation
drug substances, sterile and non-sterile drug products, analytical
test methods and devices as enablers of drug delivery.
A common problem in drug research occurs when a medicine won’t
dissolve in water and, therefore, cannot be absorbed in the body. We
found a way to use the same melt extrusion techniques that have been
used in industrial settings for centuries and apply them to medicine,
opening possibilities for the formulation of new drugs to treat
patients with a variety of diseases, from viral infections to cancer.