Adoptive T cell therapy: Harnessing the immune system to fight cancer

August 15, 2014 | by

Immunotherapy — using one's immune system to treat a disease — has been long lauded as the "magic bullet" of cancer treatments, one that can be more effective than the conventional therapies of surgery, radiation or chemotherapy. One specific type of immunotherapy, called adoptive T cell therapy, is demonstrating promising results for blood cancers and may have potential against other types of cancers, too.

In adoptive T cell therapy, T cells (in blue, above) are extracted from the patient and re-engineered to recognize and attack cancer cells. They are then re-infused back into the patient, where it can then target and kill cancer cells throughout the body. (Photo credit: Lawrence Berkeley Laboratory)

In adoptive T cell therapy, T cells (in blue, above) are extracted from the patient and modified to recognize unique cancer markers and attack the cells carrying those markers. They are then reinfused back into the patient, where they can kill cancer cells throughout the body. (Photo credit: Lawrence Berkeley Laboratory)

Here, Leslie Popplewell, M.D., associate clinical professor and staff physician in City of Hope's Department of Hematology & Hematopoietic Cell Transplantation, explains what this treatment entails.

What is adoptive T cell therapy and how does it work to treat cancer?

Every day, our immune system works to recognize and destroy abnormal, mutated cells. But the abnormal cells that eventually become cancer are the ones that slip past this defense system. The idea behind this therapy is to make immune cells (specifically, T lymphocytes) sensitive to cancer-specific abnormalities so that malignant cells can be targeted and attacked throughout the body.

Who would be good candidates for this type of therapy?

Currently, adoptive T cell therapy is mostly used to treat lymphoma and lymphoid leukemia, because these cancer cells have unique surface markers that we can reprogram T cells to recognize and attack. However, we also studying how to adapt this approach to treat other cancers as well, including myeloid leukemia, multiple myeloma and solid tumors.

What happens to the patient during this therapy?

First, we collect the patient's own T cells from the bloodstream, which takes about four hours. The cells are then modified to recognize the patient's cancer; a two- to three-week process in our laboratories. They are then frozen for later use as needed.

While the T cells are being modified, the patient undergoes an autologous stem cell transplant. Afterward, the re-engineered T cells are infused back into the patient so that they can kill any residual cancer cells that remained after the transplant. Depending on the type of cancer, its stage, the patient's health and other factors, some patients may receive the modified T cell infusions shortly after their transplant; others may get their infusions later on, when tests showed that the cancer has relapsed.

Are there any side effects to this therapy? How can they be managed?

Leslie Popplewell, M.D., says that adoptive T-cell therapy is well-tolerated by most patients, when performed in a specialized setting with experienced clinicians.

Leslie Popplewell says that adoptive T cell therapy is well-tolerated by most patients, when performed in a specialized setting with experienced clinicians.

This therapy is very well-tolerated by our patients. Side effects are generally mild and can include fevers, coughing and skin rashes, all of which can be managed with careful monitoring and appropriate intervention.

However, adoptive T cell therapy has been known to trigger cytokine release syndrome, a serious condition that can raise body temperature and lower blood pressure to dangerous levels.

This side effect has not occurred with City of Hope patients, emphasizing the point that this complex procedure should be done in a specialized setting — such as a comprehensive cancer center — with clinicians who are familiar and experienced in this approach.

What additional research is being done on adoptive T cell therapy?

Based on the positive results we have seen thus far with treating lymphoma and lymphoid leukemia, we are looking into tailoring this approach for other cancers. We currently have a clinical trial for ovarian cancer and are studying its viability for brain tumors. Both of these are difficult to treat diseases, so having a new way to target and attack these cancers will be immensely beneficial for these patients.

Do you have a question for Leslie Popplewell on adoptive T cell therapy? If so, post below.

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Learn more about becoming a patient at City of Hope by visiting us online or by calling 800-826-HOPE (4673). City of Hope staff will explain what's required for a consult at City of Hope and help you determine, before you come in, whether or not your insurance will pay for the appointment.

 


  • iwest

    Could you elaborate on some of the points in the article
    above? Specifically, the part that reads, “While the T cells are being
    modified, the patient undergoes an autologous stem cell transplant.”
    Please describe this process.

    I’m asking for clarification because my wife’s oncologist and pulmonologist here in Modesto say that autologous stem cell transplant is a
    rigorous regimen not for the feint of heart: harvesting of T-cells,
    followed by high-intensity chemo that kills all the bone marrow, followed by
    the autologous cell transplant. Requires 5-6 weeks in the hospital, and not
    recommended for older patients. Is your process different? My 59-year-old wife
    is currently in remission from mantle cell lymphoma after 10 months of chemo,
    which started with R-CHOP and finished with Rituxan-Treanda. Would she be a
    candidate for this procedure?

    Also, she’s having a lumpectomy for breast cancer Thursday, which will necessitate it’s own follow-up treatment, so not sure when we could come to Duarte for lymphoma treatment. Her oncologist had put her on “maintenance” chemo in June with revlimid, but after more than a month of that, it became obvious she could not tolerate it, and her oncologist would like her to do Rituxan again every other month for about a year if she’s not going to do another treatment.

    • H. Chung So

      Hi, please see below reply from Dr. Popplewell based on the information you’ve provided in your comment; note that more details about your wife’s diagnoses & overall health are needed before our care team can determine the best course of treatment.

      For more information about becoming a patient or getting a second opinion at City of Hope, please call us at (626) 256-4673 or visit our “Become a Patient’ page at http://www.cityofhope.org/become-a-patient.

      “We do autologous stem cell transplants on patients well into their 70s and the typical hospital stay is about 3 weeks. It does employ high dose chemotherapy and patients do need supportive transfusions. We would strongly consider transplant in a patient with mantle cell lymphoma because of the high relapse rate with that disease.

      With a recent diagnosis of breast cancer we would have to carefully examine the risks and benefits. With a recent second malignancy we could not put her on a clinical trial due to eligibility restrictions.”

      • virginia alvarado

        Do patients with p17 deletion qualify?

  • Joan Zambetti

    Are you currently using adoptive t- cell therapy in patients with a multiple myeloma and if so only in conjunction with stem cell transplants?

  • Jean Smith

    My sister has Ovarian cancer and is just starting her third round of Chemo treatment in three years. She just came out of six months of remission. Would she be a candidate for the T cell treatment? She is currently being treated at Hoag Hospital in Newport beach, CA. Should she be getting the latest greatest treatment there or would you recommend getting a second opinion at the City of Hope?

  • nebojsa grujicic

    Hi,
    Does this T cell treatment has potential to cure indolent NHL or do you see this treatment as a new way to just prolong remission? I know it is hard to give a reliable comment having in mind short period since it started and longer data will be needed, but I am interested in your opinion

    Is this treatment available for international patients? Please respond to nebojsa.grujicic@sinteza.net or if not possible, please comment here

    Best
    Nebojsa

  • Joan Zambetti

    Dr. Popplewell — please let me know if there is adoptive t-cell therapy available for
    Multiple Myeloma patients. I am preparing for a stem cell transplant at COH and want to know if t-cell or other immunotherapies are available around an ASCT.
    Thank You, Jzambetti@aol.com

  • guy fiinelo

    i am in COH now fro a second autologus stem cell transplant. the t-cell procedure seems like a viaBle addition to my transplant. how do i get more info ad discuss this with my doctor? DAY SCT-1

  • Abigail L Lasota

    Hi Leslie,
    Are you currently using adoptive T cell therapy for any lymphoma patient who may benefit from the treatment? Or is adoptive T cell therapy only used to help treat lymphoma in clinical trials?

    My husband, age 36 has double hit lymphoma (DLBC), Burkitt’s. ..After 3 cycles of Hyper C Vad chemotherapy and intrathecal injections followed by an allogenic SCT, his lymphoma relapsed after about 3 months… appearing only in the skin. No other organs have been affect at time of diagnosis nor post transplant. Our doctor is not very optimistic, however we are and I believe that my husband may bennefit from this therapy which was not offered to us as a salvage treatment. He is willing to have a second SCT if it is nessesary. Both his brothers are a 10 for 10 match! We need help!
    Thank you
    My Regards, Abigail.

  • Anthony Liberti

    Is this the same as Provenge? Sounds like it

  • Aarti Shah

    Why is this T-cell therapy given only after any autologous transplant and not instead? Secondly, do these modified T-cells divided in NK T-cells and memory T-cells and then remain in the body forever ( or for a long time). And as far as the mechanism of action goes, do they attack only lymphoma B-cells or all B-cell?