In the News

On Cancer: Cancer Immunotherapy Named Science Magazine “Breakthrough of the Year”

By Julie Grisham, MS, Science Writer/Editor  |  Monday, December 23, 2013
Pictured: T cells This image, captured by a scanning electron microscope, shows T cells (orange) attached to a tumor cell. Innovative treatments pioneered by Memorial Sloan Kettering researchers harness the ability of T cells to recognize and destroy cancer cells.

Each year, Science magazine announces one pivotal scientific achievement as the “Breakthrough of the Year.” Memorial Sloan Kettering researchers have played a leading role in pioneering this year's winner: cancer immunotherapy.

“Immunotherapy marks an entirely different way of treating cancer — by targeting the immune system, not the tumor itself,” Science said in choosing this burgeoning field. Based on the idea that the immune system can be trained to attack tumors in the same way that it targets infectious agents, cancer immunotherapy exploits the ability to harness different types of immune cells circulating in the body.

A Rich History at Memorial Sloan Kettering

Although cancer immunotherapy is being touted as a recent breakthrough in cancer treatment, its origins at Memorial Sloan Kettering go back more than a century. In the 1890s, William Coley, a surgeon at New York Cancer Hospital (the predecessor to Memorial Sloan Kettering) discovered cancer patients who suffered from infections after surgery often fared better than those who did not. His finding led to the development of Coley’s toxins, a cocktail of inactive bacteria injected into tumors that occasionally resulted in complete remission. But eventually the use of this treatment fell out of favor.

In the 1960s, research by Memorial Sloan Kettering investigator Lloyd Old led to the discovery of antibody receptors on the surface of cancer cells, which enabled the development of the first cancer vaccines and led to the understanding of how certain white blood cells, known as T cells or T lymphocytes, can be trained to recognize cancer.

Helping Patients Today

One of the pivotal milestones cited in the Science article is the work of immunologist James Allison in identifying a protein receptor on the surface of T cells called CTLA-4, which puts the brakes on T cells and prevents them carrying out immune attacks. He later identified an antibody that blocks CTLA-4 and showed that turning off those brakes allows T cells to destroy cancer in mice. (Dr. Allison, who spent nearly a decade of his career at Memorial Sloan Kettering until last year, is now at MD Anderson Cancer Center in Houston.)

Anti-CTLA-4 eventually became ipilimumab (YervoyTM), a drug approved in 2011 for the treatment of metastatic melanoma, the most deadly form of skin cancer. Dr. Allison, together with Memorial Sloan Kettering physician-scientist Jedd Wolchok, helped guide the development of ipilimumab from the first laboratory studies through the late-stage clinical trials that led to the drug’s approval.

Dr. Wolchok’s research on immune therapies for melanoma continues, including a study earlier this year that found that more than half of patients with advanced skin melanoma experienced tumor shrinkage of more than 80 percent when given the combination of ipilimumab and the antibody drug nivolumab, another promising immunotherapy drug under investigation, suggesting that these two drugs may work better together than on their own.

The other major area of research highlighted in the Science story is the development of chimeric antigen receptor (CAR) therapy, based on the idea that a patient’s own immune cell type, called T cells, can be collected from blood, engineered to recognize cancer cells and acquire stronger antitumor properties, and reinfused to circulate through the bloodstream and attack those cancerous cells. Memorial Sloan Kettering has been a leading center in developing this technology.

The first successes in this field have come in the treatment of leukemia. In March, Memorial Sloan Kettering investigators reported that genetically modified T cells had been successful in rapidly inducing complete remissions in patients with relapsed B cell acute lymphoblastic leukemia (ALL), an aggressive form of blood cancer.

“This is a very exciting finding for patients with B cell ALL, directly borne out of our basic research on CARs for over a decade, and a landmark proof of concept in the field of targeted immunotherapy,” says Michel Sadelain, Director of Memorial Sloan Kettering’s Center for Cell Engineering, who led the study, along with medical oncologist Renier Brentjens.

Memorial Sloan Kettering continues to study this approach and now has clinical trials under way investigating it in other types of leukemia, lymphoma, and prostate cancer, with several more trials slated to begin soon.

Looking toward the Future

Today, investigators in Memorial Sloan Kettering’s Immunology Program in the Sloan Kettering Institute are conducting a diverse range of studies aimed at developing the next generation of immune-based cancer treatments.

For example, Immunology Program Chair Alexander Rudensky is focused on studying a subset of T lymphocytes called regulatory T cells, which are critical for keeping other white blood cells in check and therefore play an important role in controlling immune system reactions. Understanding how these cells function, and how to inhibit them will offer novel and effective ways to treat cancer.

The research also has implications for treating conditions characterized by an overactive immune system — including autoimmune disorders such as rheumatoid arthritis, psoriasis, and diabetes.

Learn more about immunity science at Memorial Sloan Kettering.

Comments

IS HERCEPTIN therapy for sensitive ductal carcinoma of the breast a form of immunotherapy ?

Dear K Okail, thank you for your question. Herceptin is not a form of immunotherapy because it does not work by harnessing a person's immune system to fight the disease. Rather, Herceptin is a type of drug called a targeted therapy that works by targeting specific molecules involved in the development of breast cancer. You can learn more about targeted therapies for breast cancer here: http://www.mskcc.org/cancer-care/adult/breast/targeted-therapies. Thank you for your comment.

Hello,
My father had a diagnostic of lung cáncer with no posibility of surgiral intervention.
The type of cáncer is epitelial cell, no small cells.
Have you done any medical trial for this kind of cáncer? Results?
Have you plan any Medical trial for this kind of cáncer?
Is there any posibility of participate in a medical trial like inmunotherapy?
Thanks you very much and sorry about my english...

Ismael, to learn more about how we treat lung cancer, you can go to: http://www.mskcc.org/cancer-care/adult/lung If you go to that page, you'll also find a link to our list of clinical trials. To make an appointment with an MSK doctor, you can call 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment for more information. Thank you for your comment.

Are there any immunotherapy clinical trials available for metastatic squamous cell esophageal cancer? And is there data available that shows the efficacy and response rates of the various kinds of immunotherapy drugs for cancers outside of Melanoma?

Thank You.

Dear Sam, there doesn't appear to be an open trial available at MSK evaluating immunotherapy for esophageal cancer. You may try searching on the National Cancer Institute's website (www.cancer.gov) for trials at other hospitals. Here are search results for esophageal cancer trials using the keyword "immune": http://www.cancer.gov/clinicaltrials/search/results?protocolsearchid=13249969

You may be able to get more information about the efficacy of immunotherapy from the National Cancer Institute. You may call them at 1-800-4-CANCER or email them by going to this link: http://www.cancer.gov/global/contact

Thank you for your comment.

Do you have clinical trials for peritoneal cancer? Thanks

Sonia, thank you for reaching out.

You can see a list of MSK clinical trials for peritoneal cancer (most do not involve immunotherapy) here:

http://www.mskcc.org/cancer-care/clinical-trials/clinical-trial?keys=peritoneal+&field_trial_diseases_value=All&phase=All

You also might look at the US government clinical trials site for a full listing of trials for peritoneal cancer:

https://clinicaltrials.gov/ct2/results?term=%22peritoneal+cancer%22&Search=Search

Hello there,

I have recently heard about how immunotherapy can help to minimize the risk of recurrence.

My husband was diagnosed with malignant fibrous histocytoma in July 2011. He had a surgery to remove the tumor in Aug'11 followed by 36 times radiotherapy.

In Dec 2012, his cancer mets to his lungs; (1 huge in LULL, 1 tiny in RULL & 2 tiny in RLLL). He then went for 6 cycles of chemo (epirubicin & ifosfamide), 2 times of lobectomy to remove the remaining tumors and another 36 times of radiotherapy.

In May 2014, PET scan image showed tiny new lesion on his left thigh (new location). MRI done early of Aug 2014 showed the lesion has grown to more than 2cm. Biopsy was done early of Sept 2014 and it's positive for MFH.

After getting advices from several specialists between surgery & cryoablation, we have decided to go for surgery next week.

In order to prevent any other recurrence in the future; we are now looking into all treatment options that are available for MFH patients.

Questions:
1) Is/was there any immunotherapy trial done on any MFH patient(s)? If yes, is there anyway that I can get in touch with the person in charge of the trial to know more about the results?

2) Is there any plan to do immunotherapy clinical trial on MFH patients at this moment or in the near future; whether at your hospital or else where?

Note: MFH is also known as metastatic pleomorphic undifferentiated sarcoma.
Thanks.

Regards,
Intan Mansor
Malaysia

Intan, thank you for reaching out. We passed your question on to MSK physician Sandra D'Angelo, who responds:

"I’m focusing my efforts in developing immunotherapies for patients with metastatic sarcoma. Unfortunately, there are no trials currently planned in the adjuvant setting to prevent recurrence since there is limited data available that it works so far.

I am planning a phase II study of ipilimumab and nivolumab (a PD1 inhibitor which has proven to be quite efficacious in melanoma) this study is sponsored through CTEP and will be conducted through the Alliance for Clinical Trials in Oncology Cooperative group. It is due to open up in about 4-6 months."

You can learn more about the Alliance for Clinical Trials in Oncology at:

http://www.allianceforclinicaltrialsinoncology.org/main/#!

If you are interested in making an appointment at Memorial Sloan Kettering or receiving a consult, you can contact MSK's International Center at 1-212-639-4900 (http://www.mskcc.org/cancer-care/international-patients). The email address is international@mskcc.org

Finally, to look for other clinical trials for malignant fibrous histiocytoma, you can check the clinical trials site operated by the National Cancer Institute at:

https://clinicaltrials.gov/ct2/results?term=malignant+fibrous+histiocytoma

Do you treat stage1 recurrent endometrial cancer with immunotherapy?

Evelyn, there do not appear to be any immunotherapy clinical trials for endometrial cancer at present. You might contact Memorial Sloan Kettering's Immunotherapeutics Clinic (ITC) for more up to date information.

http://www.mskcc.org/cancer-care/clinical-trials/immunotherapeutics-clinic

The ITC can be reached by phone at 646-888-3359.

If you would like to make an appointment with a Memorial Sloan Kettering physician, please call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment. Thanks for your comment.

Is immunotherapy used on clinical trials only or is this available as a standard treatments as well?
Many thanks,
Fulvio

Fulvio, some immunotherapy, including the drug ipilimumab (Yervoy) discussed in this blog post, is approved by the FDA and considered a standard treatment. Other immunotherapies, such as the engineered T cells also discussed, are only available as part of a clinical trial. Thank you for your comment.

Is immunotherapy available for stage IV colon cancer mets to liver (currently deemed inoperable)

Ann, thank you for reaching out. There don't appear to be any clinical trials currently testing immunotherapy to treat liver mestastases. However, you can contact MSK's Physician Referral Service to make an appointment with a disease specialist who would then investigate with Memorial Sloan Kettering's Immunotherapeutics Clinic (ITC).

http://www.mskcc.org/cancer-care/appointment

If you are already a patient here at MSK, you can ask your primary oncologist to make a referral to the Immunotherapeutics Clinic (ITC) at Memorial Sloan Kettering Cancer Center.

Thank you for your comment.

I would like to know if you have any upcoming immunotherapy t cell trials for solid tumors in the lungs and breast cancer

J, our investigators have done research on using T cells to treat lung and breast cancers that have metastasized to the chest wall. You can read more about their work here: http://www.mskcc.org/blog/immunotherapy-shows-promise-treating-solid-tumors-chest. They hope to launch a trial for this therapy the first half of 2015. Thank you for your comment.

I am a patient at Sloan with follicular B cell lymphoma that has trans mutated in large B cell lymphoma. I was treated with bendermustine and rituximab My cancer returned and my dr wants to treat me with rchops. I will not do it. When will the trials start on lymphoma and what will the criteria be?

Steve, there is an open trial at MSK using engineered T cells for which you might qualify. The lead investigator is Craig Sauter. You should speak with your MSK treating physician about what the criteria are for the trial. Thank you for your comment.

Hi there
I've been reading with interest about the immuno drugs that you are using especially nivolumab. I see that you are now trailing it on patients with advance oesophageal cancer. Have you seen any positive results with it or is it too early in the trail status.
Thank you for your time
skye

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