David Brill
Researchers in the US have successfully treated a man’s skin cancer using laboratory-cloned T cells.
The team from the Fred Hutchinson Cancer Research Center in Seattle isolated and expanded autologous CD4+ T cell clones specific to the tumor antigen NY-ESO-1, and infused some five billion copies into a 52-year-old patient with refractory metastatic melanoma.
Computed tomography and positron emission tomography scans performed two months later showed that the patient’s tumor had completely regressed, and he remained disease free at 2 year follow-up.
His cancer had previously not responded to treatment with interferon alpha, interleukin 2 or local excision, and had spread to the groin, lung and left ilium.
Dr. Cassian Yee, who led the study, said that although the response was good in this case, more studies would be needed to confirm the efficacy of the procedure.
“This was just a small step, hopefully in the right direction,” he said, adding that the approach was only tested in patients with melanoma and the results should not be considered to apply to all cancers at this point.
The cloned CD4+ cells persisted in the patient’s blood for over 3 months without cytokine treatment – in contrast to CD8+ T cells which have been found to survive for less than 20 days without exogenous cytokines.
“Cell therapy represents a new vista in the treatment of cancer,” said Dr. Toh Han Chong, a senior consultant in the department of medical oncology at the National Cancer Centre Singapore (NCCS).
“It’s real – the fact that one patient had a long remission is great. But of course it doesn’t mean that if you treat a hundred patients all hundred will get a complete remission.”
A similar approach for patients with nasopharyngeal cancer is shortly to enter a phase II clinical trial at NCCS according to Toh, who is also an associate investigator in the laboratory of cell therapy and cancer vaccine. The trial is expected to last 3 years and will comprise 35 patients, each receiving 6 separate infusions of cloned T cells.
Writing in The New England Journal of Medicine, Yee and colleagues reported that T cells against other tumor antigens – MART-1 and MAGE-3 – were also found in the patient’s blood after the procedure, having been undetectable beforehand. This apparent extension of the immune response could explain why the tumor regressed completely despite the fact that only 50 – 75 percent of its cells expressed NY-ESO-1, the researchers said.
Nine patients were treated in all. Some others exhibited stabilization of their disease but it remains unclear why only one displayed complete regression, Yee said.
He added that T cell therapy could become more common in future, but at present the process requires very specialized equipment and training, and around 4 months is needed to grow the clones.
“Hopefully we can streamline that process a bit but it’ll never be like a drug that you can just take off the shelf,” he concluded.
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