Cell-Based Immune Therapy Shows Promise in Leukemia Patients

Pictured: Isabelle Rivière, Michel Sadelain & Renier Brentjens

(From left) Isabelle Rivière, Director of Memorial Sloan Kettering’s Cell Therapy and Cell Engineering Facility, Michel Sadelain, Director of Memorial Sloan Kettering’s Center for Cell Engineering, and medical oncologist Renier Brentjens

Doctors have traditionally had limited treatment options to offer adults with B cell acute lymphoblastic leukemia (ALL), a rapidly progressing form of blood cancer. The disease often returns, or relapses, after initial treatment with chemotherapy. At that point, patients are often resistant to additional chemotherapy and poor candidates for stem cell transplantation, which is usually effective only if the disease is in complete remission.

Now Memorial Sloan Kettering investigators report that genetically modified immune cells have shown great promise in killing the cancer cells of patients with relapsed B cell ALL. In fact, all five of the patients who have received the new therapy – known as targeted immunotherapy – have gone into complete remission, with no detectable cancer cells. The results of this ongoing clinical trial are reported online on March 20 in the journal Science Translational Medicine.

“This is a very exciting finding for patients with B cell ALL and a major achievement 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 J. Brentjens.

Engineering Precise Weapons

Targeted immunotherapy is aimed at instructing the immune system to recognize and attack tumor cells. Over the past decade, Drs. Sadelain and Brentjens, and other Memorial Sloan Kettering researchers – including Isabelle Rivière, Director of Memorial Sloan Kettering’s Cell Therapy and Cell Engineering Facility, and physician-scientist Marco L. Davila – have investigated an approach that involves removing white blood cells called T cells from patients and introducing a new gene into the cells using an engineered viral vector. Viral vectors are viruses that have been disabled so they cannot replicate and that efficiently shuttle their genetic cargo into a host cell.

After the gene is transferred and expressed, the T cells are infused back into the patient, where they multiply and cause a variety of different immune responses aimed at attacking the cancer cells. The gene used in the targeted immunotherapy for ALL codes for the creation of a receptor on T cells that enables them to recognize the CD19 protein, which is present in B cell ALL tumor cells.

Much of the early research into this approach was supported by Memorial Sloan Kettering’s Experimental Therapeutics Center and benefactors of the Center for Cell Engineering.

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A Bridge to Stem Cell Transplantation

“We have been a leading center in developing this technology in the laboratory, and we were the first center to bring this CD19-targeted approach using viral vectors to the clinic,” Dr. Brentjens explains.

In the phase I clinical trial, five patients with relapsed B cell ALL had cancer that was detectable at varying levels in the blood. After receiving the genetically modified T cells, all five patients achieved complete remission, and even highly sensitive molecular analyses found no cancer cells remaining.

“Patients with relapsed B cell ALL resistant to chemotherapy have a particularly poor prognosis,” says Dr. Brentjens. “The ability of our approach to achieve complete remissions in all of these very sick patients is what makes these findings so remarkable and this novel therapy so promising.”

Four of the five patients subsequently received additional therapy in the form of a bone marrow transplant, the standard of care for those patients who successfully achieve complete cancer remissions after treatment for relapsed disease. To date, three of the four patients have remained in remission for between five and 24 months. One patient died from complications unrelated to the cancer therapy while in remission.

“By serving as a bridge to a stem cell transplant, this therapy could potentially help cure adult patients with B cell ALL that has relapsed and who are chemotherapy resistant. Otherwise, these patients have a virtually incurable disease,” Dr. Brentjens says. “We need to examine the effectiveness of this targeted immunotherapy in additional patients before it could potentially become a standard treatment for patients with relapsed B cell ALL.”

Further clinical trials, including a phase II study, have already been planned to test whether B cell ALL patients would benefit from receiving this targeted immunotherapy along with chemotherapy earlier in the disease stage, either as part of the initial frontline treatment or after remission has been achieved to help prevent relapse.

Read a New York Times story about this new therapy and the experience of a Memorial Sloan Kettering patient.

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Commenting is disabled for this blog post.

My sister-in-law has a form of chronic leukemia which is being treated for the second time by eminent French specialists with chemotherapy. I realize this will further weaken her immune system as she has had pneumonia twice. My son is in NY and I have asked him to liase with Sloan Kettering to see if she can join one of your trials. I'm not sure which of the leukemia types she's suffering from but he will find this out and contact someone at S-K. Can you give me advice concerning this? Thank you.


if you would like to learn more about how someone can come to Memorial Sloan-Kettering as an international patient, please visit the page on our Bobst International Center at this link. http://www.mskcc.org/cancer-care/international-patients. Also, here is a link to all the clinical trials for leukemia at Memorial Sloan-Kettering:


Thank you for your comment.

My wife was diagnosed with CMML-2 early this year. She had the bone marrow transplant in June. The donor was her brother with a 10/10 match. At day 30 bone marrow biopsy, result showed all cancer cells were gone and is using 80% of donor's blood. However, after 10 more days, my wife white blood cell count was abnormal high and was diagnosed with AML. I wonder if the cell base immune therapy can apply to my wife case. Many thanks!

Dear Alfred, we cannot answer personal medical questions on our blog. If your wife would like to make an appointment with one of our specialists, please call our Physician Referral Service at 800-525-2225. They can refer her to the most appropriate physician, who can then explain what treatment options are available for her. Thanks for your comment.

I have CLL, I've been on treatment for over two years with no change. every thing stayed the same. I am currently taking Revlimid 25mg with a dose Rituxan. do back for ct scan on Dec 6, 2013. if I have not achieved good results. I don't know what's my next step. I up for a stem cell if I can get some reduction in my lymph node two at best. I was wondering if this new blood modification will work for me. I am running out of options, please HELP

Charlie, we are not able to answer personal medical questions on our blog. If you’d like to make an appointment to see a Memorial Sloan-Kettering doctor, please call our Physician Referral Service at 800-525-2225 during regular business hours or go to http://www.mskcc.org/cancer-care/appointment for more information. Thank you for your comment.

I look at progress,. never ending progress.. and from what little I know , I sometimes wonder, is cancer a physical sickness or a mental disease of the cell

Great work! I have two questions:
Are there any trials planned to test cell reprogramming in Non Small Cell Lung Cancer?
Could a child's preserved cord blood possibly be useful in her father's treatment, either in the provision of the T Cells or rebuild of his immune system?

Phil, we passed your questions on to Drs. Sadelain and Brentjens and these are their responses:

1. We are planning a trial utilizing CAR-targeted T cell in non small cell lung cancer in patients whose tumor expresses mesothelin. The trial will open in 2014 if all preparations go well and advance swiftly.

2. it would be unlikely that a child’s cord blood sample is sufficient or appropriate for a transplant in the father. However, cord blood transplant could yet be an option for the father using unrelated cord blood units.

First, I want to thank you for all the hope your studies give CA patients. My father has MDS, and was wondering if this T-cell treatment would work for him. He, like many others, would gladly be a participant in your trial studies. Thank you and God bless.

Dear Diana, we are sorry to hear about your dad’s diagnosis. Unfortunately, we can’t answer personal medical questions on the blog. If you would like to make an appointment for a consultation with one of our specialists and see if he is a candidate for a clinical trial here, please call our Physician Referral Service at 800-525-2225. Thanks for your comment.

I'm an ALL patient from Thailand. I'm interesting in your medical treatment. How can I join your treatment. Cause i don't want the chemotherapy

Nut, we are sorry to hear of your diagnosis. If you would like to make an appointment with a physician at Memorial Sloan-Kettering, please call our Bobst International Center. From outside the United States, you can use AT&T Direct Access. First dial the access number for the country you are in, then 888-675-7722. For more information, go to http://www.mskcc.org/cancer-care/international-patients
Thanks for your comment.

I have an ALL and i want this medical treatment so much. How can i join your treatment? pls reply me i just want this medical so much.

1) Do you have a provision to conduct the immunotherapy treatment for international patients? If yes, what is the way forward to get a patient admitted ?
2) In case of a pre B cell ALL, is this treatment option (immunotherapy) considered only after a relapse?

Manish, if you would like to learn about coming to Memorial Sloan Kettering as an international patient, you can contact our Bobst International Center at 1-212-639-4900 or go to http://www.mskcc.org/cancer-care/international-patients for more information. They should be able to give you more information about participating in our trials. Thank you for your comment.

Dear Mr Brentjens,

Congratulations for your results regarding to "ALL" studies.

Currently my grand mother has been diagnostic with "ALL" disease, two weeks ago. She has 83 years old.
Mr Brentjens, my Grand mother looks like well currently, but she is very tired. There is some oportunity with your treatment advantages?. At the hospital here the drs not show options for us, due to she has old, and they look for the best life quality during the next months. Drs at the hospital not suggest the quimiotheraphy.

I suppous this treatment will be expensive, but the first for me is my grand mother.

If you think that i can do anything please give me your opinion.

If there would be only one option in your hospital, i´ll study this oportunitie with my grandmother and my family.

Thanks a lot once again for your very good news for all the people involved with the "ALL" disease.

PD: Sorry for my bad english.

Rubén Darío

Dear Rubén, we are sorry to hear about your grandmother’s diagnosis. Unfortunately, we are unable to answer personal medical questions on the blog. If you would like to inquire about making an appointment or have her medical records reviewed, please call our Physician Referral Service at 800-525-2225. If you are calling from outside the United States, call our International Center by using AT&T Direct Access: dial the access number for the country you are calling from, then dial 888-675-7722. Thank you for reaching out to us.


How many of the 3 patients in this study are in remission now?

Arti, thank you for your comment. We checked with Dr. Brentjens, and he said of the five patients in this original study, two of them are still in remission. One died from a relapse of disease and two died from complications due to bone marrow transplantation.

I have a 49 year old sister who is battling T cell ALL and just heard about the success you have been having with Immunotherapy use on B cell ALL......Does this therapy work for patients with T cell ALL and if so, can you provide contact information for a consultation?
Thank you,
Phyllis Coviello

Dear Phyllis, we are sorry to hear about your sister’s diagnosis. We reached out to Dr. Sadelain with your question and he responded, “We unfortunately do not have a trial that is ready to implement this therapy for T cell ALL. The CAR technology is applicable in principle to a wide range of cancers including T cell ALL, but additional research is needed before such new trials can be implemented.”

If your sister would like to make an appointment with a Memorial Sloan-Kettering specialist for a consultation, please have her call our Physician Referral Service at 800-525-2225. Thank you for your comment.

Dear Dr. Brentjens,

It is very encouraging to learn this result about B-cell ALL study. Is this clinic trial still accepting new patients? Do you have any update of this study? And how much does a patient need to pay after joining the trial?

Thanks very much.

Wei Chen

Wei, this trial is still open and accepting patients. To learn more about participating in this or another trial, you can call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment for more information. The experts who take your call will also be able to answer questions about insurance. Thank you for your comment.

My father has t cell prolymphocytic leukemia would he be a candidate?

Justine, we are sorry to hear about your father. Please call our Physician Referral Service to find out if he would be a candidate for one of our clinical trials. They can also help you make an appointment with one of our specialists. Thanks for reaching out to us.

Dr. Spriggs mentioned in a webinar that there will be a clinical trial opening in early next year to use Dr. Brentjens T cell therapy in the treatment of ovarian cancer. How do you find out more about what the treatment will involve and who will be eligible to participate. Thank you

Dear M, thank you for your question. We reached out to Roisin O’Cearbhaill, who is involved in the study. She responds: “We hope to open a phase I safety trial for patients with recurrent ovarian cancer whose tumor stains positive for MUC16 and who have had 2-5 prior chemotherapy regimens. This is the first time that genetically modified T cells will be given into the abdomen in humans. Therefore our priority for this study is to assess the safety of this approach.”

Excellent post but I want to know if you could write a little more on
this subject? I'd be very grateful if you could elaborate a little bit more.
Many thanks!

On Sept 23 my 27 yr old son's bloodwork showed a relapse of B-cell ALL. His oncologist at Moffitt Cancer Center is contacting MSKCC to determine if you will accept our son in clinical trial NCT01044069, but I was told to reach out as well so I am using all avenues. He completed hyper CVAD therapy in Feb 2014, after diagnosis in Sept 2011. Remission was achieved in 5 weeks and remained in place over 2.5 years. No transplant done to date. thank you.

To all Doctors & researchers involved, Thank you! I am not affected, but doing research for my friend who is recently diagnosed with CLL. I am hoping you have made advances with the CAR T cells or other advances with Crispr in recent years. I am also looking for immunotherapy clinical trials for CLL in the 0 to 1 stage near Los Angeles Angeles you have any or are aware of one a colleague may be running. Thank you again for all you do, you are the true Superheroes!

Dear Melinda, we’re sorry to hear about your friend’s diagnosis. If he or she is interested in clinical trials in the Los Angeles area, we recommend going to www.clinicaltrials.gov. This is a database of trials maintained by the National Institutes of Health. Your friend may also want to look at the National Cancer Institute’s list of designated cancer centers to find an academic cancer center in Southern California. You can find a complete list here: https://www.cancer.gov/research/nci-role/cancer-centers

Thank you for your comment and best wishes to you and your friend.