Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 36
Antigens and cytokine gene in antitumoral vaccines: the importance of the temporal
delivery sequence in the antitumor signals
Maria Jose Herrero, Rafael Botella, Francisco Dasi, Rosa Algas, Maria Sanchez,
Salvador F. Aliño.
Laboratory of Gene Therapy, Department of Pharmacology, Faculty of Medicine,
University of Valencia. Avda Blasco Ibáñez, 15. 46010 Valencia-España. E-mail:
mariajoseherrero@ono.com
Different studies against cancer in the last years, including clinical trials, have shown that a
correct activation of the immune system can lead to tumor rejection but also, on the other
hand, an incorrect signalling results in no positive effects or even anergy. How the different
signals must be given to the immune system in order to get one or the other response is not
clear yet. Knowing that the genetic cell vaccines with cytokine genes as gm-csf (granulocyte
and macrophage colony stimulating factor) are the best to mediate efficient antitumoral
responses, we have worked assuming that both signals, GM-CSF and tumor antigens, are
crucial. In order to study which is the ideal temporal sequence for their administration we
have worked in a murine model of antimelanoma vaccine, with B16 cells and C57/BL6 mice,
using tumor membrane protein antigens (TMP) or whole tumor cells in combination with gmcsf
transfer before or after the antigen delivery. B16 cells were transfected using PEI
(polyethyleneimine) polyplexes (0.02 mg/ml). Tisular transfection in TMP experiments was
performed by sc. injection of 0.01 or
0.05 mg m-gmcsf in 0.5 ml saline solution. Our results show that: 1) when gmcsf tisular
transfection is performed before TMP delivery, a good dose-dependent correlation in tumor
volume decrease is observed, but with a limit effect; in contrast, when higher doses of antigen
were administered before DNA transfection, more antitumor efficacy was obtained. 2) A
similar behaviour, but with stronger positive results, was observed employing whole tumor
cells as antigens. Thus, an inefficient or efficient (total survival of treated mice) antitumoral
response was observed when DNA was administered before or after the cell vaccine,
respectively. We conclude that optimal antitumoral response can be obtained when a high
antigen signal is given before (or simultaneously) to GMCSF production, while the inversion
of the signals could result in the non desired inhibition or anergy of the immune response.
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