July 11, 2016 / All Stories

From friend to foe: when your immune system turns against you and how to turn it back

The immune system can go haywire in autoimmune diseases and cancer. While this may affect the body in different ways, the key to treating these diseases is interconnected. 

Two types of white blood cells communicating to identify and remove immune system threats.

For most, thoughts about the immune system only occur with the occasional cut, cold or flu, when healing directly depends on the immune system doing its job. And when you’re healthy, the immune system goes unnoticed, acting as the body’s security and defense system. 

A complex system of cells, tissues and organs, the immune system’s sole purpose is to recognize and keep out foreign invaders to prevent infections and diseases in the body.  

“Think of the body like the leftovers in your refrigerator, they’re going to get moldy. Our bodies don’t get moldy because our immune system recognizes many different invaders and cleans them out,” explains Diane Hollenbaugh, Ph.D., senior director, oncology discovery, AbbVie. “It is a complex task because of the different invaders and the different assaults on your body, which means your immune system has to recognize all these attacks, react and remove the threat.”

From friend to foe

However, the immune system can go haywire, betraying itself. 

“In rheumatoid arthritis, for example, the immune system is over-activated and attacks the body’s own tissue,” says Gillian Kingsbury, senior principal research scientist, immunology early discovery, AbbVie. “This attack causes inflammation in the joints that creates pain and destruction of the joint tissue.” 

In cancer, and under normal circumstances, the immune system recognizes cancerous or mutated cells in the body and responds appropriately. However, as the cancerous cells mutate and grow, they find ways to trick the immune system into ignoring them and eventually hide from the immune system altogether. 

Fiona Harding, Ph.D., research fellow, discovery oncology, AbbVie, explains, “Cancerous cells and tumors can and do stay visible to the immune system, but bring along protective gear and find ways to subvert it allowing cancer to grow in the body.”

What are the challenges the immune system faces in fighting cancerous tumors?
– Steve Davidsen, Ph.D., vice president of oncology discovery, AbbVie:

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. Some 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.


From foe back to friend

The breakdown of the immune system in autoimmune diseases and cancer may create symptoms that affect the body in different ways and to varying degrees, but the keys to treating both are interconnected. 

“Because autoimmunity and cancer can be considered as related, you are trying to either tamp down the immune system or amp it up. In cancer, you’re trying to induce the immune system to recognize the mutated cells and respond against self,” Harding says. “With autoimmunity, humans have too much response from the immune system and need to shut it down or have it regulated to a healthy level.”

“In either scenario, the targets are the same: the regulators of the immune system. But the goal differs: to turn the regulators on or turn them off,” Kingsbury says.

How are we leveraging our expertise in both oncology and immunology?
– Steve Davidsen, Ph.D., vice president of oncology discovery, AbbVie:

In many ways the two are complementary to each other. 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.

We have several examples where the oncology team investigated antagonists or agonists while the immunology team was focused on the opposite effect of the same targets. Also, many of the tools and technologies for studying the immune responses are the same, and we leverage our shared expertise, to turn it up or turn it down.

Kingsbury, Harding and others are focused on looking at these immune system switches and identify new ways that diseases for autoimmune disorders and cancer might be treated. 

It all began with one molecule, CD40, which controls how T-cells, B-cells and monocytes talk to each other. From one panel of antibodies for CD40, the team screened to see what would block the cells from talking to each other in autoimmunity, while the oncology team looked for antibodies that activated CD40 to turn on an immune response.

In another scenario, one discovery resulted in a new area of research for the oncology team. In examining PD1 as an immune system off switch that had the potential to dampen immune response, Kingsbury says, “although we haven’t been able identify what we need for immunology, we have found antibodies block the PD1 off switch and are being progressed by our oncology colleagues.”

What are the most recent advancements in immunotherapy?
– Steve Davidsen, Ph.D., vice president of oncology discovery, AbbVie:

The big breakthrough in recent years came when scientists discovered that disrupting these checkpoint receptors could activate immune cells and result in very robust anti-tumor responses. And because it works by reeducating the immune system to recognize the tumor cells, the response can last a long time. The drugs created to do this are called checkpoint inhibitors.

The potential

Scientific collaboration brings hope for patients and the future of treating these diseases.

“We have strong expertise in both immunology and oncology, and we work together to identify where there is overlap and what it means,” Hollenbaugh adds. “But the most important thing is that there is so much potential to benefit here for patients and that’s what it’s all about. The absolute potential for the patients is at the root of all of this.”

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Florian Dieckmann
Email: florian.dieckmann@abbvie.com
Call: + 1 847-937-2296
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