‘Goldilocks’ Therapies Could Be a Breakthrough for Patients with Lymphoma

March 6, 2018 | by City of Hope

breakthroughs - markus muschen Markus Müschen, M.D., Ph.D.
Lymphoma patients may soon receive treatments that leverage quality control mechanisms that our own immune systems utilize to weed out harmful antibodies.
 
“We have found a way to force lymphoma cells to fail these quality control checks so these cells become eliminated by the self-correcting forces of our own immune system,” said Markus Müschen, M.D., Ph.D., holder of The Norman and Sadie Lee Foundation Professorship in Pediatrics at City of Hope. 
 
Müschen says the concept is something that could revolutionize how patients with blood cancers are treated and, one day, cured.
 
This new approach to treating lymphoma is based on the idea that lymphoma cells originate from the B cells that produce antibodies in a patient’s own immune system.
 
“To function properly, the immune system has evolved a set of ‘rules’ that B cells have to follow,” Müschen explained. "B cells have to test their antibodies based on feedback signals. They run quality checks on their antibodies. If the antibody is too weak, it won’t sustain proliferation and survival, and the cells will die. But if the antibody is too strong, there is a checkpoint that will mark those cells for elimination as a measure of protection against autoantibodies, which would attack our own body.
 
“This checkpoint is so strict that about 95 percent of all B cells will eventually die because they fail antibody quality control. It is only a very few B cells that have their antibodies just right. Our new finding is that the exact same rules apply to lymphoma, the cancer that derives from B cells.”
 
Earlier this year, Müschen and his team discovered that B cell lymphoma cells in children and adults were bound by the same rules as normal antibody-producing B cells. Even though they are aggressive cancer cells, B cell lymphoma cells are always “reminded” of where they came from and conform to those basic rules of our immune system. That’s how they get through our checkpoints.
 
It’s the “just right” nature of these B cells that led Müschen and his team to develop what they call “Goldilocks” therapies.
 
“Our Goldilocks therapy concept is based on making drugs that force B cell lymphoma cells to fail quality checks of their antibodies,” Müschen said. “This is a major development in our lab with direct implications for therapy.”
 
The new concept and its implications for lymphoma therapy are featured in Nature Reviews Cancer. You can read the full article here.
 
In June, Müschen will be giving a talk entitled, "Autoimmunity checkpoints as therapeutic targets in B cell malignancies" at the European Hematology Association's annual meeting. Click here for more details. 
 
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