02 BOOK OF ABSTRACTS .indd

CpG oligonucleotides admixed with irradiated tumor
cells are highly efficient for the tumor prevention but
less effective for the treatment of existing tumors
Vida Stegel 1 , Andreja Kopitar 2 , Alojz Ihan 2 , Srdjan Novakovi} 1
1
Institute of Oncology Ljubljana, Department of Molecular Diagnostics, Zalo{ka 2,
1000 Ljubljana, Slovenia; 2 Medical Faculty, Institute of Microbiology and Immunology,
Korytnikova 2, 1000 Ljubljana, Slovenia
The CpG oligonukleotides could be used as immunostimulators that help the
maturation of dendritic cells - DC and lymphocytes, and consequently help to trigger
an antitumor immune response. The aim of our study was to assess the effectiveness
of tumor vaccines composed of irradiated B-16 tumor cells and CpG when used
for the prevention of tumor development or for treatment of i.p. B16 tumors. The
prevention efficacy was assessed in the experiments that were performed on the
intraperitonel (i.p.) B-16 mouse tumor model. The vaccines were administered
once or three times i.p. The average survival (AM±SD) of control animals (mock
treated) was 21.6±2.5 days. The average survival in the group of animals pretreated
with irradiated tumor cells alone was 26.6±3.7 days. The 100-days-overall survival
of animals pretreated once with irradiated B16 and 10 µg, 30 µg or 90 µg per
animal of CpG was 57%, 30% and 28% respectively. In the very same groups, the
average survival of the mice that ultimately died because of tumors was 43.3±33.0,
30.0±15.2 and 42.0±10.7 days, respectively. When the animals were pretreated with
the irradiated tumor cells and 10µg, 30µg or 90µg of CpG per animal followed by
two repeated injections of CpG only, the 100-days-overall survival was 88%, 100%
and 100% respectively.
l22
37
In the second set of experiments, the effect of the vaccine on already established
tumors was followed. The animals were first i.p. challenged with viable tumor cells,
and on the second day, treated with CpG and irradiated tumor cells. The average
survival in the group of animals treated with irradiated tumor cells alone was 20.0±9.8
days. The average survival of animals treated with one injection of 30µg of CpG per
animal was 21.0±7.2 days, while the average survival of animals treated with three
repeated injections of 30µg of CpG was 24.0±6.7 days. Similarly to achievements
in the previous groups, the treatment with one dose of irradiated tumor cells and
one injection of 30µg of CpG per animal resulted with no long-term survivors.
Average survival in this group was 21.0±6.4 days. Among the animals treated with
the irradiated tumor cells and 30µg of CpG per animal followed by two repeated
injections of CpG only, 18% of animals survived more then 100 days. The average
survival of the mice that ultimately died because of tumors was 28.0±12.2 days.
In conclusion, the tumor vaccine composed of irradiated B16 tumor cells and CpG
delays the B16 tumor development and, to a great extent, protects the animals
against tumor development. The curative treatment capacity of this kind of vaccine is
limited with the size of the tumor mass. Therefore, the tumor vaccine is more useful
for the prevention of tumor development than for the treatment of existing tumors.