
(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.
Back to topA 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.
Back to topComments
Rev. James Paul
Mar 21, 2013 • 6:04 PM
Memorial Sloan Kettering
Mar 22, 2013 • 9:46 AM
In reply to Do you have any hope for CLL by Rev. James Paul
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.”
Regina Avery
Mar 21, 2013 • 7:27 PM
Memorial Sloan Kettering
Mar 24, 2013 • 9:17 AM
In reply to Are there any similar studies by Regina Avery
Charlotte K. Hays
Mar 21, 2013 • 8:21 PM
Memorial Sloan Kettering
Mar 24, 2013 • 9:11 AM
In reply to I would like to know if by Charlotte K. Hays
Cydni L Ryen
Mar 21, 2013 • 9:46 PM
Memorial Sloan Kettering
Mar 22, 2013 • 9:47 AM
In reply to I have leiomyosarcoma and by Cydni L Ryen
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.
Melissa Donovan
Mar 22, 2013 • 12:45 AM
Memorial Sloan Kettering
Mar 24, 2013 • 9:09 AM
In reply to Is this a potential treatment by Melissa Donovan
Dr. Steve Chen, US Natioanl Academy Of Engineering
Mar 22, 2013 • 2:37 AM
Memorial Sloan Kettering
Mar 24, 2013 • 9:16 AM
In reply to Can this same therapy by Dr. Steve Chen, US Natioanl Academy of Engineering
Sheena Jain
Mar 22, 2013 • 5:14 AM
Memorial Sloan Kettering
Mar 24, 2013 • 9:18 AM
In reply to Do you think this treatment by Sheena jain
Robert
Mar 22, 2013 • 9:51 AM
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.”
Catherine Hepprich
Mar 22, 2013 • 10:35 AM
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
Memorial Sloan Kettering
Mar 22, 2013 • 11:46 AM
In reply to I have lung and bone cancer by Catherine Hepprich
Gerald L. Morelock
Mar 22, 2013 • 2:07 PM
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?
Memorial Sloan Kettering
Mar 22, 2013 • 2:13 PM
In reply to I am fighting Multiple by Gerald L. Morelock
Thank you for your comment. You can find a list of our current clinical trials and eligibility criteria for multiple myeloma here: http://www.mskcc.org/cancer-care/clinical-trials/clinical-trial?keys=&f….
Jim Henninger
Mar 22, 2013 • 3:31 PM
Judy Tartell
Mar 22, 2013 • 3:59 PM
Memorial Sloan Kettering
Mar 24, 2013 • 9:19 AM
In reply to Is this treatment for ALL by Judy Tartell
Linda DeBoer/ Caregiver
Mar 22, 2013 • 4:32 PM
Carole Healey
Mar 22, 2013 • 4:54 PM
Ann Lang
Mar 22, 2013 • 5:07 PM
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!
Barbara Danback
Mar 22, 2013 • 5:17 PM
Memorial Sloan Kettering
Mar 24, 2013 • 9:14 AM
In reply to Is this therapy going to be by Barbara Danback
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.”
Olga Brandt
Mar 22, 2013 • 5:18 PM
Katherine H Boone
Mar 22, 2013 • 5:41 PM
Memorial Sloan Kettering
Mar 24, 2013 • 9:20 AM
In reply to I have a grandson 27 years by Katherine H Boone
Robert Santoro
Mar 22, 2013 • 6:31 PM
American Cancer Fund
Mar 22, 2013 • 7:28 PM
Gary Lineberger
Mar 22, 2013 • 7:40 PM
Edward V. Mase
Mar 22, 2013 • 8:07 PM
Memorial Sloan Kettering
Mar 23, 2013 • 8:45 AM
In reply to Last year I was diagnosed by Edward V. Mase
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.
MRS JILL DAVIS MORRA
Mar 22, 2013 • 8:18 PM
Memorial Sloan Kettering
Mar 23, 2013 • 8:34 AM
In reply to WHAT ABOUT THE PATIENTS THAT by MRS JILL DAVIS MORRA
If you’d like more information about our treatments for pancreatic cancer, please go to: http://www.mskcc.org/cancer-care/adult/pancreatic If you’d like to learn about clinical trials for pancreatic cancer, you can visit our clinical trials page: http://www.mskcc.org/cancer-care/clinical-trials/clinical-trial?keys=pa… Thanks for your comment.
Gena Main
Mar 22, 2013 • 8:19 PM
Carola Fischer
Mar 22, 2013 • 8:44 PM
Marcie Amihod
Mar 22, 2013 • 8:44 PM
Brandon Davidson
Mar 22, 2013 • 9:08 PM
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. :)
Sincerely,
Brandon Davidson
Mary Klinke
Mar 22, 2013 • 9:57 PM
John Rowe
Mar 22, 2013 • 10:58 PM
Shelley Dodt
Mar 22, 2013 • 11:10 PM
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.
Reta Krukowski
Mar 23, 2013 • 3:06 AM
Annie
Mar 23, 2013 • 4:01 AM
Xiechen
Mar 23, 2013 • 9:21 AM
Thanks for your comment. You can find our information for international patients here: http://www.mskcc.org/cancer-care/international-patients.
Elsa. Monroe
Mar 23, 2013 • 9:38 AM
Do you have any hope for CLL patients?