Zinnia Parra Guillén(1), Pedro Berraondo(2), Benjamin Ribba(3) Iñaki F. Trocóniz(1)
(1) Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy, University of Navarra (Spain); (2) Division of Gene Therapy and Hepatology, Center for Applied Medical Research (CIMA), University of Navarra, Spain, (3) NUMED project-team, INRIA Grenoble-Rhône-Alpes, Montbonnot- Saint Ismier, France.
Objectives:. A vaccine vector that targets the human papillomavirus 16 E7 antigen to dendritic cells, has shown potent immune response against tumour cell lines expressing E7 antigen in a murine model of cervical carcinoma. However a decreased in the response was observed as the time between tumour cell injection and vaccination increased [1]. The aim of the study is to develop a population model in mice able to describe tumour growth dynamics and the effect the vaccine on tumour size to better understand the mechanisms implied.
Methods: 5×105 tumour cells expressing HPV16-E7 proteins were injected into the shaved back of C57BL/6 mice in 200uL of PBS. A single dose of 50ug of vaccine or PBS (control group) was intraperitoneally administered to mice, but on different days after tumour inoculation. Tumour size presented as the average of two perpendicular diameters (mm) was measured at regular intervals. Mice were euthanatized if tumour size reached 20mm.
Results: The model developed presented the following main components: (i) Tumour progression in the animals receiving saline injection was described with an exponential model, (ii) vaccine effects were modelled assuming that vaccines triggers a non-instantaneous immune response inducing cell death. Delayed response was described with a series of transit compartments [2], and (iii) a tolerance effect dependent upon tumour size was also incorporated. A small percentage of treated animals showed, after a period of an apparent complete tumour remission, a relapse. Relapsing was tackled considering a mixture model at the level of the vaccine to trigger the adaptive immune response, and more mechanistically assuming a small but permanent memory immune response.
Conclusions: A population model able to describe the different vaccination protocol outcomes has been successfully developed. Data required of model complexities at both the typical/structural population, and the stochastic level.
References:
[1] Berraondo P et al. Cancer Res 67:8847-8855, 2007
[2] Savic RM et al. J Pharmacokinet Pharmacodyn 34:711-726, 2007
Reference: PAGE 21 (2012) Abstr 2581 [www.page-meeting.org/?abstract=2581]
Poster: Oncology