Study Combines PD-1 and CAR-T Immunotherapy to Treat Mesothelioma

Dr. Prasad Adusumilli

At the 2019 American Society of Clinical Oncology annual meeting, Dr. Prasad Adusumilli from Memorial Sloan Kettering Cancer Center shared exciting new results from his study on combination immunotherapy for malignant pleural mesothelioma.

Among the 18 mesothelioma patients in the study, 14 received a combination of two different immunotherapy treatments. Eleven of this group experienced a complete response, a partial response or stable disease.

The latest results from this phase 1 clinical trial were presented June 4. They demonstrate the promise of using two immunotherapy approaches at one time.

Phase 1 studies are designed only to test the safety, side effects, best doses and timing of a new treatment, not cure cancer. They typically include patients not helped by other treatments.

Still, the results are encouraging and pave the way for further research on combining two distinct types of immunotherapy to treat aggressive, incurable cancers.

Targeting Mesothelin from Two Angles

Mesothelin is a protein found on mesothelioma and other cancer cells. Researchers have been searching for ways to help the human immune system better recognize mesothelin and attack the cancer cells displaying it.

To leverage the immune system against mesothelioma, the researchers combined CAR T-cell therapy and PD-1 drugs.

CAR T-cell therapy begins with collecting a patient’s own immune cells. These T-cells are then engineered in the lab to better recognize a specific feature — in this case, mesothelin — on a patient’s tumors.

The modified immune cells are infused back into the patient where they go to work attacking and destroying cancer displaying the mesothelin protein.

PD-1 inhibitors limit cancer’s ability to block immune cells from attacking it. This bolsters the immune system’s ability to recognize and kill cancer.

By first priming each patient’s immune T-cells to hone in on mesothelin, then removing cancer’s brakes on the immune system with PD-1 drugs, the approach provides a unique way to attack aggressive tumors from two angles.

Latest Mesothelin Study Results Are Positive

The ongoing study first began in May 2015 and is slated for completion in April 2020. The investigators have been presenting encouraging results from the study along the way.

The latest findings provide data that a much more effective treatment for mesothelioma is a realistic possibility.

Adusumilli, deputy chief of thoracic service and co-director of the mesothelioma program at Memorial Sloan Kettering in New York, provided the latest update at the June 2019 meeting in Chicago. He is the study’s principal investigator.

He shared that two patients experienced complete metabolic response. This means a PET scan cannot detect any metabolically active cancer at the time of the test. Some doctors call this a complete remission.

Nine Study Participants Continue to Beat the Odds

In addition to those remarkable outcomes, five study participants experienced a partial response and four had stable disease during a median follow up of 31 weeks.

Partial response means tumors shrank but did not completely disappear. Stable disease refers to tumors that do not grow during the study period.

Given the average survival for people diagnosed with malignant pleural mesothelioma is around 12 months, any ability to shrink tumors or stop the growth of this aggressive cancer is a positive finding.

“Encouraging antitumor activity of MSLN-targeted CAR T-cell therapy was observed when combined with anti-PD1 therapy and shows promise for future development of this approach.” the authors wrote.

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Oncology Medical Writer

Suzanne Dixon is a registered dietitian, epidemiologist and experienced medical writer. She has volunteered with the National Cancer Policy Forum, Oncology Nutrition Dietetic Practice Group, American Institute for Cancer Research, American Society for Clinical Oncology, The National Academies of Sciences, Engineering, and Medicine. The New York Times and Time Magazine also have reviewed her cancer patient resources.

2 Cited Article Sources

  1. Adusumilli, P.S. et al. (2019, June). Regional delivery of mesothelin-targeted CAR T cells for pleural cancers: Safety and preliminary efficacy in combination with anti-PD-1 agent.
    Retrieved from: https://abstracts.asco.org/239/AbstView_239_269679.html
  2. Clinical Trials.gov. (2019, May 17). Malignant Pleural Disease Treated With Autologous T Cells Genetically Engineered to Target the Cancer-Cell Surface Antigen Mesothelin. Retrieved from: https://clinicaltrials.gov/ct2/show/NCT02414269

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