Abstract
The existence of inherited aggressive forms of medullary thyroid carcinoma (MTC) and
their resistance to classical therapies make it a prime candidate for adoptive immunotherapy.
Highly potent antigen-presenting cells, namely dendritic cells (DCs), may serve as
an interesting tool for anticancer vaccination. Here we report on the in vitro findings of a vaccination trial in five MTC patients, who were treated with a new
DC generation protocol consisting of granulocyte-macrophage colony-stimulating factor
and interferon-α (IFN-DCs). These cells were pulsed with tumor-specific calcitonin
and administered twice. In two patients who responded to therapy we found a large
increase (in mean 2.9±1.9%) of antigen-specific IFN-γ-secreting CD4+ cells as well
as an increase of granzyme B positive CD8+ cells (mean 2.2±0.2%) in the peripheral
blood. In parallel, a decrease of CD4+/CD25+/FoxP3+ regulatory T cells was seen. Importantly,
in vitro stimulation of PBMC with 10 different 15mer calcitonin peptides resulted in the identification
of two HLA class II epitope regions within the central part of full-length calcitonin.
These data were in accordance with the results drawn from the computer-based algorithm
epitope prediction software SYFPEITHI. Measurement of different pro- and anti-angiogenic
factors did not allow for a distinct outcome of prediction of the treated patients.
In summary, we have demonstrated that immunization with IFN-DCs leads to a tumor epitope-specific
immune response in MTC patients and may, therefore, represent a promising tool for
future vaccination trials.
Key words
dendritic cells - interferon-α - immunotherapy - medullary thyroid carcinoma - calcitonin
- epitopes
References
in vitro generation cells.
Horm Metab Res.
2008;
40
99-107
Correspondence
schottmt@uni-duesseldorf.de
