Treatment with Dendritic Cells Leads to Long-Term Mesothelioma Survival in Small Studies

Three small studies suggest that dendritic cells may offer a new, more promising way to fight malignant pleural mesothelioma. 

Dendritic cells are immune system cells that function as messengers. They are supposed to signal T-cells to attack cancers like malignant mesothelioma.

But mesothelioma cells can keep dendritic cells from doing their job. The result is that the number of activated T-cells around mesothelioma tumors stays low and the tumors keep growing.  

Now, Dutch researchers studying the problem say a vaccine made from dendritic cells may hold the answer. They analyzed the results of three small dendritic cell studies. These studies included a total of 29 mesothelioma patients. 

Some of the patients in these studies lived much longer than mesothelioma patients normally live. If these results can be replicated in a larger trial, it could be a hopeful sign for mesothelioma patients everywhere.

Dendritic Cells and Immunotherapy for Mesothelioma

Malignant pleural mesothelioma is an asbestos-linked cancer on the tissue around the lungs. Tumors on this multi-layer pleura are hard to remove and hard to treat. Most mesothelioma patients start with systemic chemotherapy, but it does not usually help for more than a few months. Nine months is average survival for a person with pleural mesothelioma. 

Until 2020, Alimta was the only approved mesothelioma drug. In 2020, the FDA approved an immunotherapy combination of Yervoy and Opdivo for mesothelioma treatment. But even these drugs have limited effectiveness. This is partly because there are so few T-cells in mesothelioma tumors for them to activate. 

Treatment with dendritic cells could change that. Dendritic cells can turn an “immune desert” with low T-cell infiltration into an environment rich with cancer-fighting immune cells.

It’s done by removing some of a mesothelioma patient’s own dendritic cells (or using lab-grown cells). These cells are “activated” by exposure to tumor-associated antigens. Then, the patient gets an injection of these activated cells. If it works, the patient’s own immune system will start working against their tumor. 

Promising Mesothelioma Survival

The new report focused on three Phase I/II studies of mesothelioma therapy with dendritic cells. The first two studies used cells from the patients themselves to create the vaccine. The third study used mesothelioma cells grown in a lab. 

The studies involved 29 people with pleural mesothelioma. Patients received treatment with dendritic cells between 2006 and 2015. 

By the time the study ended, the median overall survival was two years and three months. More than 55 percent of patients were still alive at two years. One in five was still alive at five years. This is almost unprecedented survival for people with pleural mesothelioma.

The Dutch researchers say this long-term mesothelioma survival is “promising”. The results of these small studies form the basis for a new, larger study. That study, called DENIM, is currently enrolling mesothelioma patients. 

Source:

Dumoulin, D, et al, “Long-Term Follow-Up of Mesothelioma Patients Treated with Dendritic Cell Therapy in Three Phase I/II Trials”, May 19, 2021, Vaccines, https://www.mdpi.com/2076-393X/9/5/525