Researchers describe the first successful use of a human patient's cloned infection-fighting T cells as the sole therapy to put an advanced solid-tumor cancer into long-term remission. A team led by Cassian Yee, M.D. (pictured), an associate member of the Clinical Research Division at Fred Hutchinson Cancer Research Center reported these findings.
Yee and colleagues removed CD4+ T cells, a type of white blood cell, from a 52-year-old man whose Stage 4 melanoma had spread to a groin lymph node and to a lung. T cells specific to targeting the melanoma were then expanded vastly in the laboratory using modifications to existing methods. The lab-grown cells were then infused into the patient with no additional pre- or post-conditioning therapies, such as growth-factor or cytokine treatment. Two months later, PET and CT scans revealed no tumors. The patient remained disease free 2 years later, when he was last checked.
"We were surprised by the anti-tumor effect of these CD4+ T cells and its duration of response," Yee said. "For this patient we were successful, but we would need to confirm the effectiveness of therapy in a larger study."
Yee cautioned that these results represent only one patient with a specific type of immune system whose tumor cells expressed a specific antigen. More studies are needed to confirm the effectiveness of the experimental T-cell therapy. If proven successful in more patients, Yee predicted this therapy could be used for the 25 percent of all late-stage melanoma patients who have the same immune-system type and tumor antigen.
Using a patient's own immune system to combat cancer, called immunotherapy, is a growing area of research that aims to develop less-toxic cancer treatments than standard chemotherapy and radiation.
The patient in the journal report was one of nine patients with metastatic melanoma who were being treated in a recently completed clinical trial to test dose-escalation of autologous CD4+ T cells. Earlier studies performed by Yee used CD8+ T cells, which do not persist in the body without the support of CD4+ T cells or growth factors such as interleukin 2. Yee and colleagues theorized that infusion of a massive dose of CD4+ T cells would persist longer in the body because they make their own growth factor, interleukin 2, while stimulating the anti-tumor effect of the patient's existing CD8+ T cells. However, until recently there was no feasible way to isolate and expand anti-tumor CD4+ T cells in the lab.
The researchers were successful in all of these areas. The patient received a dose of 5 billion cloned CD4+ T cells with specificity for the melanoma-associated NY-ESO-1 antigen. The cells persisted for at least 80 days in the patient's body. And, even though only 50 percent to 75 percent of the patient's tumor cells expressed the NY-ESO-1 antigen, the entire tumor regressed following the infusion. The scientists postulated that the patient's immune response was broadened to other antigens expressed by the tumor cells. Follow-up tests showed T-cell responses to two additional tumor antigens, MAGE-3 and MART-1.
Illustration: Fred Hutchinson Cancer Research Center.
Read more…
Fred Hutchinson Cancer Research Center News Release (06/18/08)
MedPage Today w/audio clip (06/18/08)
EurekAlert! (06/18/08)
Medical News Today (06/19/08)
Science Daily (06/19/08)
Abstract (New England Journal of Medicine; Vol. 358, 25, 2698-2703 (06/19/08))