For the first time, doctors have put a man's melanoma into remission after they injected him with his own tumour-killing immune cells.
Researchers at the Fred Hutchinson Cancer Center in Seattle, led by Dr. Cassian Yee, said that the man remained cancer-free at his last check-up, 26 months after being treated.
The report detailing this breakthrough is published in the June 19 issue of the New England Journal of Medicine.
The 52-year-old man had not responded to conventional treatments and his stage four melanoma, a type of skin cancer, had spread to a lymph node in the groin and to one of his lungs. Doctors drew blood from him and then isolated known tumour-killing cells. These cells were cloned to increase their numbers and then re-injected into the man.
The patient was not given any subsequent treatment.
"We were surprised by the anti-tumour effect of these cells and its duration of response," Yee, an associate member of Fred Hutchinson's clinical research division, said in a statement.
"For this patient we were successful, but we would need to confirm the effectiveness of therapy in a larger study."
Melanoma is a type of skin cancer that starts in the melanocytes. Melanocytes make melanin, which give colour to the skin.
The Canadian Cancer Society's Canadian Cancer Statistics 2008 report estimates that about 4,600 new cases of melanoma will be diagnosed in Canada this year.
Yee cautioned that if the findings are duplicated in other late-stage melanoma patients, they would only apply to those patients with the same type of immune system and who produce the same tumour-killing cells.
However, the findings add to the growing research into immunotherapy, which involves using a patient's own immune system to treat cancer. Immunotherapy breakthroughs will result in cancer treatments that are less toxic to the human body than chemotherapy and radiation.
Summary:
Treatment of Metastatic Melanoma with AutologousCD4+ T Cells against NY ESO-1
Naomi H. Hunder, M.D., Herschel Wallen, M.D., Jianhong Cao, Ph.D., Deborah W. Hendricks, B.Sc., John Z. Reilly, B.Sc., Rebecca Rodmyre, B.Sc., Achim Jungbluth, M.D., Sacha Gnjatic, Ph.D., John A. Thompson, M.D., and Cassian Yee, M.D.
We developed an in vitro method for isolating and expanding autologous CD4+ T-cell clones with specificity for the melanoma-associated antigen NY-ESO-1. We infused these cells into a patient with refractory metastatic melanoma who had not undergone any previous conditioning or cytokine treatment. We show that the transferred CD4+ T cells mediated a durable clinical remission and led to endogenous responses against melanoma antigens other than NY-ESO-1.
CD8+ cytotoxic T cells can be harvested from a patient with cancer, expanded in vitro, selected for specificity against a tumor-associated antigen, and infused back into the patient. Such autologous T cells have been shown in clinical trials to have a beneficial effect in some patients with cancer. The cytotoxic antitumor effect of CD8+ T cells depends on CD4+ T cells, which provide CD8+ T cells with growth factors such as interleukin-2 and can mediate the destruction of tumor cells either directly or indirectly.6-9 Growth factors like interleukin-2 can act in an autocrine manner, which in principle would allow an infusion of CD4+ T cells to proliferate in the patient and stimulate endogenous antitumor CD8+ T cells. Until recently, however, a means of isolating and expanding antitumor CD4+ T cells in numbers sufficient for cellular therapy has not been feasible. The identification of HLA class II-restricted epitopes in tumor associated antigens such as NY-ESO-1 and tyrosinase and the development of methods for the isolation and expansion of CD4+ T cells in vitro gave us the opportunity to implement a clinical trial to evaluate the safety, in vivo persistence, and antitumor efficacy of autologous CD4+ T-cell clones for the treatment of metastatic melanoma. We describe a patient with refractory metastatic melanoma who entered long-term complete remission after receiving autologous NY-ESO-1-specific CD4+ T-cell clones.
