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Tumor-reactive memory T cells and their activation<br />
in cancer patients<br />
Volker Schirrmacher and Philipp Beckhove<br />
German Cancer Research Center, Division of Cellular Immunology, 69120 Heidelberg,<br />
Germany<br />
Antigen-specific memory T cells could be an ideal source for effective immunotherapy<br />
of cancer since they show higher frequencies and exert stronger immune responses<br />
than naïve T cells. Our previous studies revealed that tumor reactive memory T<br />
cells are enriched in the bone marrow (BM) of mice and humans. Such cells have<br />
cell-surface markers that characterize them as either central or effector memory T<br />
cells. They can be restimulated ex vivo by autologous dendritic cells loaded with<br />
tumor-associated antigens (TAA) to produce interferon-γ and to become cytotoxic.<br />
Restimulated human memory T cells but not naïve T cells infiltrated autologous<br />
tumor but not normal skin transplants and caused tumor-regression after transfer<br />
into tumor-xenotransplanted NOD/SCID mice. The therapeutic efficiency of memory<br />
T cells was augmented upon co-transfer of TAA presenting dendritic cells.<br />
We will provide data indicating that pre-existing memory T cells from cancer patients<br />
can be reactivated also in situ by antitumor vaccination when using the virusmodified<br />
live cell vaccine ATV-NDV. ATV-NDV stands for autologous tumor vaccine<br />
modified by infection with Newcastle Disease Virus (NDV). Results from clinical<br />
trials of antitumor vaccination with ATV-NDV will be presented. They demonstrate<br />
augmentation of memory T cell responses and augmentation of long-term overall<br />
survival of patients in Phase II studies.<br />
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