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VIEW ALL NEWSHuman regulatory T cell depletion enhances cancer vaccine response
NEW YORK (Reuters Health) - Depletion of human regulatory T (Treg) cells enhances antigen-specific responses to cancer vaccines, according to a report in the August 1st issue of Blood.
Dr. Michael A. Morse from Duke University Medical Center, Durham, North Carolina and colleagues investigated the effects of an immunotoxin targeting Treg cells (denileukin diftitox) on antigen-specific responses to immunization with a vaccine against carcinoembryonic antigen (CEA) in 15 patients with advanced CEA-expressing malignancies.
Depletion of Treg cells led to enhanced T-cell proliferation in vitro, the authors report. T-cell responses against self and foreign recall antigens were also enhanced.
Repeated denileukin diftitox dosing of the 14 patients with colorectal cancer and one patient with breast cancer resulted in consistent decreases in Treg cells, the researchers note, and 13 of 14 evaluable patients had a CEA-specific immune response at some point during their immunizations
Although antibodies to the fowlpox vector were detected at similar titers in all groups after vaccination, CEA-specific antibodies were more frequent in patients receiving a single dose of denileukin diftitox
"The effect of the denileukin diftitox on antibody responses against CEA is surprising," the investigators say. "It would appear that multiple doses have no effect on the antibody response to the foreign antigen (the fowlpox vector), but they cause a reduction in the self-antibody (CEA) response."
"These results indicate the potential for combining Treg-cell depletion with anticancer vaccines to enhance tumor antigen-specific immune responses and the need to explore dose and schedule of Treg depletion strategies in optimizing vaccine efforts," the authors conclude.
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