In the Clinic

On Cancer: New Trial Advances Cell-Based Immune Therapy for Certain Leukemias

By Julie Grisham, MS, Science Writer/Editor  |  Thursday, February 20, 2014
Pictured: Renier Brentjens, Isabelle Rivière & Michel Sadelain (From left) Investigators Renier Brentjens, Isabelle Rivière, and Michel Sadelain

A new Memorial Sloan Kettering study evaluating a cell-based immune therapy to treat an aggressive form of leukemia reports that 88 percent of patients responded to the treatment. It is the largest study to date to evaluate this treatment for adult patients with B cell acute lymphoblastic leukemia (ALL), a rapidly progressing form of blood cancer.

ALL is a disease that often returns, or relapses, after initial treatment with chemotherapy. At that point, patients are often resistant to additional chemotherapy and are poor candidates for bone marrow or stem cell transplants, which are usually effective only if the disease is in complete remission.

The first study of this approach, published in March 2013, treated five patients. The current study, which was published this week in Science Translational Medicine, treated an additional 11 patients. “This study is important because it demonstrates that this is a repeatable outcome,” says Renier Brentjens, one of the study’s senior authors. “Often when we are developing new therapies, the results for the first few patients look very positive, but the results are not repeatable with larger groups of patients.”

A New Paradigm for Treatment

The new treatment, known as targeted immunotherapy, is aimed at instructing the immune system to recognize and attack tumor cells. The approach involves removing a type of white blood cells called T cells from patients and introducing a new gene into the T cells that enables them to recognize the cancer. After the gene is transferred and expressed, the T cells are infused back into the patient, where they multiply and cause a variety of immune responses aimed at attacking the cancer cells.

Michel Sadelain, Director of Memorial Sloan Kettering’s Center for Cell Engineering and a senior author of the study, developed the technique. Over the past decade, Drs. Sadelain and Brentjens, along with Isabelle Rivière, another senior author of the study and Director of Memorial Sloan Kettering’s Cell Therapy and Cell Engineering Facility, and other Memorial Sloan Kettering researchers, have investigated this approach.

“Chimeric antigen receptors, or CARs, are a new class of drugs in oncology,” says Dr. Sadelain. “They instruct immune cells collected from the patient to identify and eliminate tumor cells. The engineered cells persist in the patient long enough to induce substantial tumor regression and eventually a complete remission, acting like a ‘living drug’ and patrolling the body in search of tumor cells to eliminate.”

The researchers report in the current study that 14 of 16 total treated patients responded to the new therapy. The majority of these patients either already had or eventually will undergo follow-up stem cell transplants. However, some patients are not able to undergo transplants because they are not well enough, and others choose not to have additional treatment.

“Transplants are still the standard of care,” Dr. Brentjens says. “But as more patients get this engineered immune therapy treatment, and not all of them are able to go on to get a transplant, we’re getting an increasing number of patients we can follow over time who we hope will remain in remission for the long-term without the transplant.”

He adds that cell-based immune therapy could eventually become the new standard of care, allowing patients to avoid transplants altogether.

Managing Side Effects

In addition to reporting outcomes for the 16 patients, the study looked in detail at the most common side effect of the treatment, known as cytokine release syndrome (CRS). CRS occurs when the engineered T cells reach the cancerous cells and release proteins called cytokines, which the T cells use to fight the leukemia. Symptoms of CRS include high fevers, low blood pressure, and changes in mental status such as confusion or agitation.

“CRS is an indication that the treatment is working, and so far it’s been fully reversible,” Dr. Brentjens explains. “So these toxicities are not something that we want to prevent, but we want to be able to minimize and manage them.”

“It’s important to remember that we have no guidelines for this technology. It’s completely uncharted territory,” he adds. “As this treatment expands to more centers — and we’re sure that it will — other physicians will need to understand why these side effects arise and have a paradigm for how to manage them.”

“There is still much more for us to learn,” Dr. Brentjens concludes. “Right now we are basing everything we know about this treatment on only 16 patients.“

Expanding Availability of Cell-Based Treatments

“What makes the CAR technology so attractive is the potential to apply it to a wide range of cancers,” says Dr. Sadelain. “We reported over a decade ago that a molecule called CD19 could serve as a target for CAR therapy against leukemia. This insight is validated by today’s results in B cell cancers, especially ALL. We are now exploring other molecules that likewise could be targeted by CAR therapy to treat lung, ovarian, prostate, and other cancers.”

“One important feature that distinguishes Memorial Sloan Kettering from most other academic centers is our ability to translate our conceptual innovation and preclinical modeling to bring them to first-in-man clinical trials, as was the case for this ALL study,” says Dr. Rivière. “Clinical studies like this one are made possible by a visionary commitment to establishing specialized facilities such as the Cell Therapy and Cell Engineering Facility.”

In November 2013, Drs. Sadelain, Brentjens, and Rivière co-founded a new biotechnology company called Juno Therapeutics. The Seattle-based start-up is aimed at speeding the development of novel immunotherapies for cancer.

Memorial Sloan Kettering currently has trials under way evaluating cell-based immune therapies in chronic lymphocytic leukemia, B cell non-Hodgkin lymphoma, prostate cancer, and the pediatric form of ALL.

Additional trials are planned for other types of cancer, as well as a phase II study for B cell ALL, but it is too early to say when those studies may be open to patients.

This research was supported by the Terry Fox Foundation, the American Society of Hematology-Amos Medical Faculty Development Program, the Alliance for Cancer Gene Therapy, the Carson Family Fund, the Major Family Fund for Cancer Research, Joel and Yvette Mallah, the Lewis Sanders Fund, the Damon Runyon Cancer Research Foundation, Kate’s Team, Mr. William H. Goodwin and Mrs. Alice Goodwin and the Commonwealth Cancer Foundation for Research, and the Experimental Therapeutics Center of Memorial Sloan Kettering.


Will it work on Mutiple myeloma ?

William, there are currently no trials to evaluate this approach in multiple myeloma. If you'd like to learn about the trials that we do have for multiple myeloma, you can go to To make an appointment to speak with a Memorial Sloan Kettering doctor, you can call 800-525-2225. Thank you for your comment.

I am writing on behalf of my husband who has Triple Hit Diffused Large B-Cell Lymphoma. I want to know if he would benefit from this trial? He has exhausted chemo therapy.

Cheryl, there is a trial evaluating this mode of therapy in some patients with B cell lymphoma. To learn more about the trial, 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.

Since 2011 my wife was diagnosed with Acute Lymphoblastic Leukemia and she was treated with several protocols with chemoterapy, but she didn't reach more than 6 month of remission. At this time, she's again on treatment with new chemoterapy but I'm afraid she does not respond this new treatment. On the begining of the treatment she had serious problem with infection by fungal on both lungs, and till now she takes every day antifungal medicin (itraconazol). Is it possible to treat in this case with this new therapy?

Gelson, unfortunately we are not able to answer personal medical questions on our blog. To find out about being treated for ALL at MSK, you or your wife can call 800-525-2225 or go to for more information on making an appointment. Thank you for your comment.

My husband has been treated this past year for high grade MDS with Vidaza.
I just heard about this new treatment and would like to know if it might be applicable to patients with MDS.

Cecile, the modified T cell therapy is not currently being evaluated for MDS. If you would like to make an appointment to speak with a Memorial Sloan Kettering doctor about treatments that might be right for your husband, you can call 800-525-2225 or go to for more information. Thank you for your comment.

Is targeted immunotherapy given in conjunction with chemotherapy regimes or in place of them?

Is there a pediatric trial in progress?

Are these trials being conducted at other centers? UK? Australia?

Mel, thank you for your questions. We checked with Drs. Brentjens and Sadelain, and they said that patients in the trial receive additional salvage chemotherapy followed by the T cell therapy.

There is one pediatric trial open for ALL. You can find information about the protocol on our website at

These trials are not being conducted in the UK or Australia right now. There are plans for a trial in the UK, but it will not be ready to open for some time.

My cousin is a 68 year-old female who is in good health except for cancer. She had breast cancer, chemotherapy and a double mastectomy. Now she has non-small cell stage 4 lung cancer. Can this T-cell therapy be used for this cancer? Can you help her? We are desperate to prolong her life.

Brigitte, there are plans to eventually test this therapy in lung cancer, but we don't know when those trials will begin. To learn about trials that Memorial Sloan Kettering currently has open for lung cancer, you can go to If your cousin would like to make an appointment to speak with a Memorial Sloan Kettering doctor, she can call 800-525-2225. Thank you for your comment.

I am suffereing from colorectal cancer. Is there a possibility that this new therapy can be applied to the cancer cells responsible for colorectal cancer. Also, your description of the side effects of this new therapy appear to be somewhat confusing. As to the severity of the side effects and how to control the side effects. Can the side effects result in terminal conditions? Any idea of what the long term effects of introducing this enhanced T-cell into the body; will it create a brand new type of cancer cell even worse than the one it is attempting to kill? In the case of a patient with a cancerous tumor, would this type of therapy not only kill all cancer cells but also remove the need to surgically remove the tumor?
And lastly , does this new type of surgery shed any light on finding an actual cure to cancer; preventing the original creator of the cancer cell from creating the cancer cell?

George, thank you for your questions. There is not currently a study to evaluate the modified T cell therapy in colorectal cancer.

In the studies that have been done so far, the side effects from the treatment were treatable and reversible.

Because this research is at an early stage, it is too early to know what all the long-term effects will be and whether this therapy will be effective against solid tumors.

It is also too early to know whether this treatment will ultimately result in a cure for any type of cancer.

I have a friend who is suffering from metastatic breast cancer. Is there a possibility that this type of therapy can be adapted to breast cancer?

Patrice, this type of immune therapy is not currently being evaluated for breast cancer, but it's possible that it will be in the future. If your friend would like to learn about current trials for metastatic breast cancer at Memorial Sloan Kettering, she can go to Thank you for your comment.

Dear Sirs,

I thank you and further encourage you to carry on this impressive work.

My father is currently struggling with recently diagnosed AML. Is there a trial in the works for AML using this technique? If there's not one in Sloan Kettering, do you know of any place in which they are currently performing (or planning) one such trial?

Thanks in advance and keep up the good work.

Dear Eugenio, we are sorry to hear about your father's diagnosis. We sent your inquiry to Dr. Sadelain, and he responded, "We are conducting research to apply this approach to AML but do not have a trial open for this type of leukemia at this time."

For your information, here is a listing of the clinical trials we do have open for patients with AML:

If you would like to make an appointment to have your father consult with one our specialists and learn whether he is eligible for one of our trials, please call our Physician Referral Service at 800-525-2225. Thank you for your comment.

I am currently in early 50 and was diagnosed with PH+ CML 4 years ago and currently in completed remission with just a medication (Tasigna). I was told I would have to be on the medication for rest of my life. Is there a plan to expend T-cell treatment for CML patience as well?

Dear Frank, there are no trials currently underway using this technique in patients with CML. Here is a link to the trials we do have for CML:

If you would like to make an appointment with one our specialists, please call our Physician Referral Service at 800-525-2225. Thank you for reaching out.

Thank you very much for speedy response.
I will definitely check out the link.

I was diagnosed in Dicember 2011 with All Ph+. After taking Sprycel and two induction chemoteraphy, I underwent BMT from HLA-identical related donor in July 2012. I did not have a complete molecular response and, after three months taking Ponatinib (Iclusig), I was relapsed in December 2013. Now, after another chemo, I’m waiting to receive DLI infusion. Can this new treatment works in the case of ALL-Ph+ patients after BMT?

Antonella, unfortunately we are unable to answer specific medical questions on our blog. 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 In addition, you can see a list of trials available at Memorial Sloan Kettering for ALL at

Thanks for your comment.

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