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Metastatic Melanoma Patients Respond to Novel T-Cell / Dendritic Cell Immunotherapy
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Despite having metastatic melanoma that had spread to her lungs, Robin (Nicho) Bourque, age 37, is still working as a clinical laboratory manager in her home town of Lake Charles, Louisiana, taking care of her three school-age children, and enjoying ski trips with her family. Since January 2009, Bourque has experienced a 57 percent shrinkage of her tumors, thanks to receiving 115 billion T cells augmented by dendritic cells pulsed with MART peptide, in a novel phase II immunotherapeutic clinical trial. Patrick Hwu, MD, chair of the Department of Melanoma at M. D. Anderson, is also the study chair of this innovative clinical trial; Nicholas Papadopoulos, MD, a co-investigator, is Bourque’s medical oncologist and winner of the 2008 Melvin L. Samuels Award for Excellence in Patient Care; and Priscilla Miller, RN, is manager of the clinical protocol.
No Other Treatment but at M. D.Anderson
When Bourque’s melanoma was first found in August 2008 on a finger by her dermatologist in Lake Charles, she was told that her cancer was rare, and “they wouldn’t accept any other treatment but at M. D. Anderson.” She was referred first to surgical oncologist Merrick Ross, MD, who initially spared as much of her finger as possible to enable her to continue to type for her job but later found deeper disease and had to amputate more of the finger. She was referred to Dr. Papadopoulos in August 2008 when cancer was found in a lung. “When Dr. Papa gave me eight different options for treatment, I asked him, ‘If I were your daughter, what would you choose for me?’” Dr. Papa recommended interleukin-2, an FDA-approved T-cell growth factor with potent anti-tumor activity. When two rounds of IL-2 alone proved insufficient to control her disease, Bourque had surgery to remove tumors in her lung, then started on the T cell/dendritic cell protocol along with high-dose IL-2 in January 2009 administered on the inpatient unit.
Prior to receiving T cell infusions, Bourque received cyclophosphamide then fludarabine chemotherapy to deplete her normal lymphocytes in order to make space for more rapid multiplication of the adoptive tumor-infiltrating lymphocytes (TILs). The TILs were derived from her resected tumors and expanded in M. D. Anderson’s Good Manufacturing Practices (GMP) Laboratory to produce enough tumor-reactive cells that have the ability to recognize specific antigens on the surface of melanoma cancer cells and kill them. The chemotherapy pretreatment was added to prevent her own regulatory or suppressor T cells from interfering with the repopulation and activity of the infused TILs, enabling the TILs to muster a larger and more effective attack against melanoma cells. Dendritic cells loaded with the MART-1 antigen were added after T-cell infusion because they are the most potent antigen-presenting cells known while having the greatest capacity to activate T cells that are capable of destroying tumors. High-dose IL-2 was also administered after T-cell infusion to enhance expansion and activation of the T cells.
Bourque decided to try an investigational therapy for two reasons. "I knew the value of research because I work in a research lab," she said, "I know I’m going through this for a reason, and that’s to help other people in the future. If I don’t do it, you won’t know if it’s going to work." More effective treatments are urgently needed for metastatic melanoma, Dr. Hwu noted, as the five-year survival rate averages less than two percent.
First to Benefit from Dendritic Cell Vaccine
Bourque was the first patient in the study to receive dendritic cells as well as T cells. Since then, only one other patient has qualified to receive dendritic cells, as patients must have MART-1 antigens as well as HLA-A2 to participate in this arm of the study. Patients without MART-1 may enroll in the T-cell arm of the trial. No normal tissues (except melanocytes) or other cancer cells except melanoma express the MART-1 antigen, making this an ideal targeted therapy for specifically attacking melanoma cells, long known to be highly immunogenic. The two therapies are expected to be synergistic when combined, as dendritic cell immunization significantly proliferates adoptively transferred T cells, inducing long-term regression of aggressive tumors in lab models.
Bourque is not the only patient with metastatic melanoma to benefit from this innovative immunotherapy. Ten patients enrolled in the trial by February 2009 have responded positively to the therapy. Tumor shrinkage found on CT scan 12 weeks after TIL infusion ranged from 9.2 percent (stable disease) to 60 percent (partial response). It is too soon to determine response in the three patients enrolled in February, April, and May, as well as how many patients will sustain complete responses, especially over time. However, Dr. Hwu expects to see more complete and durable responses as perfection of T-cell expansion enables infusions of increasingly more T cells (recently expanded from 8 billion to 130 billion), and as more patients experience the synergistic benefit of also receiving antigen-pulsed dendritic cells.
Bourque’s advice to other patients who may be thinking about trying a clinical trial? "I want people to know that you can do this; you can beat this," she said, "It’s important to do it or you won’t know if it can help others."
Like Part of the Family
"I would definitely come back here for any treatment," Bourque concluded. "The staff at M. D. Anderson treat you like you are part of their family; they want you to get better. It’s important to live every day like it’s the last, and they worked around our schedule so we could even go snow skiing."
For more information about this clinical trial, please contact Dr. Patrick Hwu at 713-563-1728, phwu@mdanderson.org, or Priscilla Miller at 713-563-9445, pmiller@mdanderson.org. For information about the numerous other clinical trials offered for melanoma, please go to http://www.mdanderson.org/education-and-research/departments-programs-and-labs/departments-and-divisions/melanoma-medical-oncology/clinical-trials/index.html
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