Cell-Based Immune Therapy Shows Promise in Leukemia Patients


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.

Do you have any hope for CLL patients?

We spoke with Drs. Sadelain and Brentjens who said: “Our results to date are better in ALL compared with CLL. We attribute this to the fact that the patient T cells we engineer are remarkably effective against leukemia in the bone marrow, but less so in the lymph nodes. We are preparing a clinical study to evaluate T cells that we believe will be more effective against disease in the lymph nodes. We are seeking funding to initiate this study in CLL. We continue to enroll patients on two other CLL clinical trials, which have resulted in some promising but far less dramatic clinical outcomes.”

Are there any similar studies planned or underway for AML patients who've already had a stem cell transplant and are out of remission?

Thanks for your comment. Dr. Brentjens says: “At this time, I’m not familiar with any such trials, although we’re working in the lab on generating a receptor to target AML tumor cells. Unfortunately, we don’t expect such a trial to open for several more years.”

I would like to know if similar trials are planned for Advanced Breast Cancer. I have stage IV ER+PR+ breast cancer with spread to bones and liver. I would be greatly interested in any trials that may possibly benefit me

Thanks for your comment. We spoke with Dr. Brentjens, who says that there are plans to conduct a clinical trial in certain types of breast cancer. However, he anticipates that approval for this trial is still at least a year away.

I have leiomyosarcoma and have been told I have a year and a half to live. Would this therapy work for me? I am willing to come to New York to learn more.

This therapy is currently being studied for patients with B cell ALL. If you would like to make an appointment with a Memorial Sloan-Kettering physician, please call 800-525-2225.

Is this a potential treatment for CML. Please let me know

Thanks for your comment. We spoke with Dr. Brentjens, who says that unfortunately this is not currently a therapy designed to treat CML.

Can this same therapy approach apply to late stage Large B-Cell Lynphoma cancer treatment? If yes, are you interested in clinical trials on real patients?

Dr. Brentjens says: “Yes, we’re close to opening up another clinical trial to treat high risk B cell lymphomas. We expect this trial to open in the next 1-2 months, wherein therapy is combined with a prior autologous stem cell transplant.”

Do you think this treatment is of any help to ovarian cancer patients, where the cancer has spread to the peritoneal regions?

Dr. Brentjens says: “We hope so. We’re currently working in the lab to develop a similar treatment strategy for patients with relapsed ovarian cancer. We anticipate opening this trial hopefully by early next year.” Thanks for your comment.

How long will the clinical trials take? I was diagnosed with this cancer oct 27th 2012, knowing that I can use this safely in the next 5 years if I relapse will be a huge relief... Is this possible?

Thanks for your comment. Dr. Brentjens says: “The current clinical trials will likely take another two to three years, and hopefully thereafter we’ll be able to provide this therapy outside of a clinical trial. So hopefully yes, if God forbid your disease relapses, this therapy should still be available.”

I have lung and bone cancer and received chemotherapy.The treatment is not helping,but it is making me very weak and I lost a lot of weight.Would the Cell Based Immune Therapy be available for my kind of cancer?Is there a hospital closer to Florida where I live,that has the same treatment available.Looking foward to get your professional answer.Thank you!
Catherine Hepprich

Thank you for your comment. Unfortunately, we cannot answer personal medical questions about treatments for particular patients on our blog. This treatment is currently being studied in patients with B cell ALL.

I am fighting Multiple Myeloma cancer. I have had two autologous stem cell transplants and I am currently doing well. I am very interested in any trials involving the use of immunotherapy. I understand a lot is being focussed upon leukaemia and the protein that is out of balance. But I haven`t heard of any pursuits toward mm in this area. Are such trials taking place? And if so, what is the criteria for inclusion to these trials?

I'm very happy to see scientific breakthroughs in your research. Great work! Sincerely, Jim Henninger (Former patient of Dr Bosl, 1992/1993)

Is this treatment for ALL being considered for young children?

Dr. Brentjens says: “Yes. We’re currently obtaining approval to treat a subset of children with B cell ALL. We hope to open up this trial by June of this year.” Thanks for your comment.

I lost my husband last February 2012 with AML. The advances that have broken thru are amazing and so filled with hope for other leukemia patients and their families that it has recharged the hopes and prayer of all involved. GOD BLESS

Congratulations to Dr. Brentjens and the brilliant research team at MSK. Thank you for dedicating your lives to finding a cure.
Carole of Kate's Team (Terry Fox Run)

My late husband and my 2 children, one whose life was lost to cancer at age 18 in 2007, all have battled Li-Fraumeni Syndrome. Our daughter is an Pre-B Cell ALL survivor of 13 years. I can not even begin to thank you and all scientists working around the globe on the cancer treatments and cures, such as this one, that are being discovered.
You bring hope to millions who are frightened, lighten the burden of those grief loss and keep the spirits of those who lost their battles alive because you live the quote "What we do in life echoes in eternity".
Thank you!

Is this therapy going to be available for relapsed follicular lymphoma?

Thanks for your comment. Dr. Brentjens says: “We have an open clinical trial which includes treatment for some types of relapsed follicular lymphoma. Please contact the Leukemia Service at 212-639-5279 for more information.”

I don't have the leukemia but am realy happy for those who do, it is refreshing to here really good news these strange days we live now.Olga.

I have a grandson 27 years old that was born with Diamond Blackfan Syndrome He has lived on Prednisone all of his life. For some reason that has helped the body make the red blood cells that have kept him alive Do you have any updated information that would help him?

Dr. Brentjens says: “Unfortunately, this therapy is not designed to treat Diamond Blackfan Syndrome, and I don’t foresee that this approach could provide any benefit in this disease.” Thanks for your comment.

Good Job Gang, keep working

Great job! keep up the great research.

any chance one of these geniusees start working on a cure for als

Last year I was diagnosed with metastatic prastate cancer. I am receiving hormone therapy and radiation in my shoulder. Is there any hope of your kind of therapy that would be helpful to me? If not, can you give me some direction. Many thanks

Hi, Edward. We do have one trial under way that is looking at modified T cells for the treatment of prostate cancer. You can find more information here: http://www.mskcc.org/cancer-care/trial/09-036 If you’d like to make an appointment at Memorial Sloan-Kettering, please call 800-525-2225. Thanks for your comment.


So glad to hear this to many ppl die from this disease and any other cancer we need to find a cure to help these ppl....:)

I surely hope that this therapy somehow can also help young children with Leukemia, and THANKS for your GREAT WORK, God's Blessings for you future work.

MSK was the only hospital that finally diagnosed me 10 yrs.ago.They saved my life just knowing what kind a rare cancer I had. Still being treated but so greatful to them. I am want to them thank them for continuing there research and hard work.

You guys have done something GREAT. This is a huge scientific breakthrough and a miracle for people with Lukemia. My aunt: Gina Giallombardo, died of Rhabdomyosarcoma in 2011 and was treated at MSK and she almost won her battle because of the great nurses and staff and just everyone there. Unfortunately, her horrible cancer relapsed and she died May 12, 2011. But thx to you guys, he had a good time being treated there. PLEASE keep up this good work with the immunotherapy. And although I'm not a scientist or anything (I'm an 11 year boy), but as a suggestion, has anyone ever thought of gene therapy to the immune system cells.Because their genetic material could be injected immune cells can destroy cancer cells only. Thank You. :)

Brandon Davidson

Most wonderful news, and maybe a door is opening got much more.

My son died of exactly B-cell ALL Leukemia a year ago.....I sure wish I had this connect then..... I miss him terribly. He's not even buried yet. I'm sick.

We are at the beginning of a new era in immunotherapy. Please support the clinical trials and research. Our scientists do know how to make cancer a lessor killer but they need our support. Look up cancer vaccines in google and follow the progress. In 5-10 yrs chemo will be obsolete. I got a cancer vaccine 4 yrs ago and no one in my trial has had it return.

This is great news for everybody that has it. I just hope it makes it through the trials quickly and becomes available for all that have that type of cancer. Thank you all for the work you do to save people.

Thank you so much for your patience ... My prayers are with you for continued success.


I come from CHINA and i am an APL patient , I consult for APL immunotherapy meaningful?

This article is an encouragement! Glad to read this awareness is spreading.