From Friend to Foe: When Your Immune System Turns Against You and How to Turn it Back

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.”
 

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.”

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.

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.”

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.”

Through this collaboration, four compounds are being investigated for oncology and one for inflammatory bowel disease and lupus, and are progressing to early stage clinical trials later this year.

Learn more about our pipeline.