Monitoring of DC and T cell functions in healthy controls and patients with prostate cancer treated with GM-CSF transduced allogeneic vaccines and anti-CTLA-4

Prostate cancer is a relatively common cancer in the Netherlands. If the tumor
is localized, cure can only be achieved by surgery or locoregional
radiotherapy. In case of metastatic disease hormonal therapy and chemotherapy
are the first treatment options. These therapies can control the disease for a
relatively long period, but are not able to cure prostate cancer. A novel
strategy is immunotherapy, that is aimed to stimulate the immune system of the
patient against his own cancer. Immunotherapy for prostate cancer is still
experimental and the first results are very promising, particurlarly in
patients with low residual disease and a rising PSA.

We recently conducted a phase I/II trial in castrate resistant prostate cancer
using a allogeneic vaccine, producing GM-CSF (GVAX) and anti-CTLA-4 antibodies
(ipilimumab). The whole treatment lasted 24 weeks and 28 patients were
included. The primary endpoint was safety and tolerability. Secundary endpoints
were tumor response, survival and immune response. We hope to identify markers
which can predict the clinical efficacy of this immunotherapy. We observed an
increased T cell activation (HLA-DR levels on CD4+ and CD8+ T cells) and
dendritic cell activation (CD40 op CD11cpos/CD14neg/BDCA1pos dendritic cells
(DC)) in blood of treated patiënts, suggesting a GVAX/ipilimumab induced
effect. Moreover, we observed clear differences of these cells in prostate
cancer patients as compared to a small group of healthy controls.

To determine the frequency of activated T cells and dendritic cells in healthy
controls:

Twelve healthy volunteers will be asked to donate 20 ml blood. PBMCs will be
isolated and by FACS analysis the following markers will be measured on
dendritic cells and T cells:
a) peripheral blood dendritic cells and monocytes:
1) CD1c high/CD14neg/BDCA1+ cells (cDC1)
2) CD1c high/CD14neg/BDCA3+ cells (cDC2)
3) CD1c high/CD14low/MDC-8+ cells (cDC3)
4) CD1c neg/CD14neg/BDCA2+ cells (plasmacytoid cells (pDC)) en
5) CD11c+/CD14+ monocytes.
b) peripheral blood CD4+ en CD8+ T cells (CD3, CD4, CD8, CD45RA, CD45RO, CD27,
CD25, and HLA-DR, CTLA-4, PD-1) en regulatory T cells (CD4+/CD25high/FoxP3+)

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