Cancer Drug Reawakens Failed Immunotherapy for 6 Patients

For patients with advanced multiple myeloma, a breakthrough immunotherapy called CAR T cell therapy can buy precious time, but eventually cancer cells learn to hide from the engineered immune cells hunting them. Now researchers at Technical University of Munich have figured out how the cancer pulls off this disappearing act and found a way to stop it.

CAR T cell therapy works by reprogramming a patient's own immune cells to recognize and destroy cancer. In multiple myeloma, these engineered cells hunt for a molecule called BCMA on the surface of malignant cells. But over time, the therapy stops working as BCMA mysteriously vanishes from the cancer cells' surface, making them invisible to the treatment.

Dr. Leonie Rieger and her team discovered the culprit: a cleanup system inside cells called the ubiquitin-proteasome system was breaking down BCMA. Scientists previously thought this system only worked inside cells, but the new research published in Blood shows it can also strip away molecules from the cell surface.

The team realized they already had a tool to fight back. Carfilzomib, a drug already approved for multiple myeloma, blocks this breakdown system. In lab experiments and animal studies, the drug successfully prevented BCMA from disappearing.

Then came the real test. The researchers treated 10 patients whose CAR T cell therapy had failed. After receiving carfilzomib, all 10 patients showed BCMA back on their cancer cells' surface. Six patients, those who still had enough engineered immune cells circulating in their bodies, saw their therapy become effective again.

The Ripple Effect

This discovery could reshape how doctors use immunotherapy. Prof. Florian Bassermann's team is now investigating whether giving carfilzomib right from the start of CAR T cell therapy might prevent the cancer from hiding in the first place.

The implications stretch beyond multiple myeloma. The researchers believe this same breakdown system might be stripping other target molecules from cancer cells in different types of immunotherapy. If they're right, this approach could help countless patients whose cutting-edge treatments have hit a wall.

Dr. Judith S. Hecker, who leads Cellular Immunotherapy at the hospital, acknowledges the study's small size means more research is needed to identify which patients will benefit most. Larger clinical trials are already being planned.

For now, six patients have gotten something increasingly rare in advanced cancer: a second chance at a treatment that had already failed them once.