Immunotherapy Shows Promise for Treating Solid Tumors in the Chest

By Julie Grisham,

Wednesday, November 19, 2014

Michel Sadelain and Prasad Adusumilli

A study in mouse models suggests how modified T cells may be used to treat tumors in the area just outside the lungs.

In 2013, Science magazine named cancer immunotherapy the scientific breakthrough of the year. It featured two active fields of study at Memorial Sloan Kettering as leading areas of research.

One of those fields is chimeric antigen receptor (CAR) therapy, which is based on the premise that a patient’s own immune cells can be trained to recognize and attack cancer cells. This approach has shown early potential in treating certain kinds of blood cancer, but researchers have yet to determine the best way to apply it to treating solid tumors.

A study published earlier this month in Science Translational Medicine suggests how this technique might be applied to tumors of the pleural cavity, the area in the chest found just outside the lungs. The pleural cavity is the most common location in the body for rare, aggressive tumors called mesotheliomas and is also a frequent site of metastasis for other tumor types, including lung and breast cancers.

“Every year in the United States, about 150,000 new patients are diagnosed with cancer in the pleural cavity, and about 1.5 million procedures are done as a result of these tumors,” says MSK thoracic surgeon Prasad Adusumilli, the first author of the new study. “I’ve focused much of my work the past several years on finding better ways to treat these tumors.”

Finding the Right Target

In CAR therapy for leukemia, immune cells called T cells are genetically engineered to recognize the CD-19 protein, which is found on the surface of blood cells called B cells. Since CD-19 is not present in pleural tumors, investigators needed to identify another target — a protein that’s present in these tumors yet not in most other cell types — in order to protect healthy cells from attack.

They found these attributes in a protein called mesothelin. Mesothelin is present in almost 90 percent of mesotheliomas, as well as 60 percent of lung adenocarcinomas and 35 percent of triple-negative breast cancers (the most difficult-to-treat type of breast cancer). Previous studies conducted by the MSK team showed that the presence of mesothelin indicates that a cancer is more aggressive and less likely to respond to other treatments, such as radiation or chemotherapy.

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Putting the Pieces in Place

For the CAR therapy research to move forward for pleural tumors, the investigators spent several years developing mouse models that closely mimic this type of cancer — the first ever developed.

They also focused on finding ways to manufacture T cells engineered to recognize the mesothelin protein, work led by MSK’s Cell Therapy and Cell Engineering Facility under the direction of Isabelle Rivière.

CAR T cell therapy works by filtering out a patient’s T cells and — outside the body — introducing a new gene into the cells. That gene encodes a receptor that enables the T cells to recognize a protein present on the surface of cancer cells — in this case, the mesothelin protein.

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A Superior Immune Response

In CAR therapy for leukemia, the engineered cells are reintroduced to the patient through the bloodstream, but for pleural tumors the investigators found another way.

“We thought this was going to be a pretty run-of-the-mill animal study, but it turned out to yield a big surprise,” says Michel Sadelain, Director of MSK’s Center for Cell Engineering and the study’s senior author. “We discovered that when we infused the T cells directly into the pleural cavity, the response was 30 times better than infusing them intravenously. The intrapleural infusion was superior in terms of eliminating local tumors, and it yielded a superior overall immune response.”

“We learned that when we administer the T cells directly into the pleural cavity, they all see the cancer immediately,” Dr. Adusumilli adds. “The T cells get activated and divide more quickly. Furthermore, they are able to enter the bloodstream and travel throughout the body, finding and killing cancer cells that are present in other locations.”

In the majority of mice, the tumors were eradicated and didn’t come back. And two further experiments — conducted 100 or 200 days after the mice had been infused with T cells — showed that the immune cells had persisted and still were able to kill the cancer when new tumors were introduced.

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Moving Forward to Trials

Based on the mouse studies, the investigators plan to launch a clinical trial in early 2015 to find out if the treatment is safe for people with solid tumors in the chest cavity.

“Ultimately, patients are the reason we do this research,” Dr. Sadelain concludes. “I’m very proud to work at MSK, where we can develop this kind of approach in the research lab and implement it in the clinic, thanks to our facilities and the depth of our clinical programs.”

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This research was funded by the American Association for Thoracic Surgery Third Edward D. Churchill Research Scholarship; the Experimental Therapeutics Center at MSK; William H. Goodwin and Alice Goodwin; the Commonwealth Foundation for Cancer Research; the Lake Road Foundation; the National Institutes of Health and the National Cancer Institute under grants R21 CA164568-01A1, R21 CA164585-01A1, 2T32CA9501-26A1, and P30 CA008748; the US Department of Defense under grants PR101053 and LC110202; and the Stand Up To Cancer-Cancer Research Institute Immunotherapy Dream Team. Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research.


Hello, first of all, thanks for all your hard work and dedication; you truly are heros. Does your research and/or planned clinical trials involve the sequencing of the tumor's genome in order to identified cells from the immune system that may attack a specific mutation in the malignant cells? Is gastro-esophageal cancer considered a solid tumor in the pleural cavity, and as such be a potential candidate for your upcoming trials? Thank you.

Edwin, thank you for your comment and questions. According to Dr. Adusumilli, "Our institutional immunotherapy research does include identifying tumor mutation targeting immune responses. While the pleural tumors from gastroesophageal cancers are not included in our upcoming clinical trial, we are conducting preclinical work in this area with a goal to translate it into trials in near future."

Good Evening: I am interested in finding out about possible enrolling in this upcoming trial. I have been a patient at msckk for two years. i have triple negative breast cancer which has metastized to my spine and lungs. I recently participated in a trial which was stopped by the sponsor due to the the fact that all patients enrolled were not responding. I am considering participating in a trial run by Dr. Monchok which involves immunotherapy which is an intravenous infusion. Is there anyone I can speak to to find out if and when I can participate in this trial? My oncologist is Dr. Tiffany Traina, who helps me find trials that she thinks are appropriate for me. I thank you for all that your staff does to help and support their patients. Thank you so much and I look forward to hearing from you.

Joyce, since you are already a patient of Dr. Traina's, we recommend you speak with her about which trials may be right for you. Thank you for your comment.

I was operated for thymoma by Dr Bains on 6th August . Pleurectomy with decorticaton was done. would you enroll such patients to avoid recurrence with this kind of therapy.

Muneeb, we forwarded your question to Dr. Adusumilli, who responded, "Patients with thymoma are not included in our protocol. Patients with thymic cancer are potential candidates for mesothelin-targeted immunotherapy in future protocols." Thank you for your comment.

I am stage 4 rectal patient with nothing else left for me to try. My rectal cancer mestasized to the lung area. Would I be eligible for this trial.

This trial is for patients with mesothelioma, breast cancer, or non-small lung cancer whose tumors express a particular protein, called mesothelin. To find out about trials MSK has open for advanced rectal cancer, you can call our Physician Referral Service at 800-525-2225 or go to for more information on making an appointment. Thank you for your comment.

My husband has just begun remission from small cell lung cancer, extensive. He will soon begin brain radiation as a prophylactic. Is there any new work being done to prevent the recurrence of his cancer?

Currently in a trial at Duke University Cancer Center. Methylgene 265. NSCLC. Have been through chemo & both upper lobes removed in 2014. Cancer came back in left lower lobe in Oct 2015. After second scan cancer was seen about the size of grains of sand (3). Third scan showed it had grown & according to doctors my only option was a trial drug as mentioned earlier. Surgery, etc. is not advisable. I know you would need all medical records to advise if you could offer other treatments. I am a very active, healthy 68 yr old female. All lab work shows I am right where I need to be with no complications. No health issues other than controlled BP. I am hoping there is something out there for me. The trial drug side effects are brutal & feel due to not being able to eat I will die due to malnutrition therefore I am going to
Withdraw from this trial. With best regards.

I now have Stage 4 non small cell adenocarcinoma. A very early metastasis was to a lymph node located just under the pulmonary artery and my heart. It has not responded to radiation or chemotherapy and has sent out cancer cells almost everywhere using pathways of the lymphatic system. I believe my best chance for some quality time--no cure, I understand--would be an immunotherapy or targeted genetic therapy. Do you know where any Medicare approved studies might be found for me???

Dear Thelma, we are sorry to hear that your cancer has spread. Clinical trials are testing immunotherapy drugs in all settings, including as a first-line therapy in patients with advanced lung cancers, and in patients who have previously received chemotherapy.

To browse through and learn more about our clinical trials investigating immunotherapy (and other treatments) for people with advanced non small cell lung cancer, please visit…

If you have any questions about these trials or would like to make an appointment for a consultation with one of our specialists, please call our Physician Referral Service at 800-225-2225. Thank you for reaching out to us.

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