Dendritic Cell Therapy for Mesothelioma: Can it Help Other Treatments Work Better?

A new kind of mesothelioma treatment called dendritic cell therapy might make other types of treatments even more effective. 

Right now, chemotherapy with Alimta (pemetrexed) is the only approved therapy for malignant mesothelioma. Many others are in the works. But so far, none of them extend the lives of mesothelioma patients by more than a few months. 

Dendritic cell therapy for mesothelioma may be different. This novel treatment uses the patient’s own cells to jumpstart the immune system. 

A Dutch company developed and is testing the new treatment. The data so far suggests that it could boost chemotherapy and help new drugs like Keytruda work better. 

How Dendritic Cell Therapy Works

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 tumors can suppress the action of dendritic cells. This keeps the number of activated T-cells in the tumor low. This may be one reason that immune checkpoint inhibitors (like Keytruda) are only moderately effective for mesothelioma. 

The new dendritic cell therapy developed by Amphera attempts to get around the problem. The patient’s own dendritic cells are removed, “reprogrammed”, and injected back into the patient. If it works, these altered cells prompt NK-cells, B-cells, and T-cells to start attacking mesothelioma cells.  

According to the company, “Amphera’s DC therapy MesoPher has demonstrated that it can induce a T-cell response in mesothelioma, and therefore could enable checkpoint inhibitor therapy.”

MesoPher as a New Mesothelioma Treatment

The FDA and Europe’s EMA have granted orphan drug status to MesoPher. Orphan drugs are promising drugs designed to treat very rare diseases like mesothelioma. 

In a recent test of dendritic cell therapy, patients received MesoPher prior to treatment with an immune checkpoint inhibitor. Key findings were presented at the American Association for Cancer Research annual meeting this spring. They showed a disease control rate of 88 percent in nine mesothelioma patients. 

“Amphera’s unique approach to dendritic cell therapy can turn ‘cold’ tumours with immune suppressing environment into ‘hot’ tumours infiltrated with cytotoxic T-cells,” says Amphera CEO Rob Meijer. Meijer says this “makes MesoPher an ideal component of combination treatment with checkpoint inhibitors in mesothelioma.”

In another study, 230 pleural mesothelioma patients are getting MesoPher for “maintenance” after chemotherapy. 

Patients get 3 bi-weekly injections of MesoPher along with best supportive care. They get extra doses at weeks 18 and 30. The main goal is to determine if chemotherapy patients live longer with dendritic cell therapy than without it.

“This phase II/III trial will determine whether DC therapy in patients with MPM is safe and effective as a maintenance treatment and subsequently might be a new treatment option for MPM,” writes lead author Robert Belderbos.

Sources:

Belderbos, R, et al, “A multicenter, randomized, phase II/III study of dendritic cells loaded with allogeneic tumor cell lysate (MesoPher) in subjects with mesothelioma as maintenance therapy after chemotherapy: DENdritic cell Immunotherapy for Mesothelioma (DENIM) trial.”, June 2019, Translational Lung Cancer Research, pp. 280-285, http://tlcr.amegroups.com/article/view/29434/21555

“Amphera presents data of MesoPher and checkpoint inhibitor combination therapy to treat mesothelioma at AACR 2019”, April 2019, Amphera news release, https://www.amphera.nl/amphera-presents-data-of-mesopher-and-checkpoint-inhibitor-combination-therapy-to-treat-mesothelioma-at-aacr-2019/