In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 24, No. 18_suppl ( 2006-06-20), p. 12507-12507
Abstract:
12507 Background: Electrochemotherapy (ECT), consisting of electroporating cytotoxic agents (bleomycin or cisplatinum) in tumors, is effective in inducing destruction of cutaneous or subcutaneous tumors and can be used as a palliative treatment for patients with skin melanoma metastases. Our objective was to combine the antigen release induced by ECT with a potent and adapted stimulation of the innate immune system in order to induce a systemic anti-tumor response. Methods: The preclinical work was performed on murine models of skin tumors: fibrosarcoma (LPB) and melanoma (B16F10). We found that electrochemotherapy induced the recruitment of immune cells expressing CD11-c and Mac-1 in the first 48h after the treatment. By quantitative RT-PCR, we showed that this immune cell infiltrate was associated with an increase of TLR9 RNA expression. Therefore, we decided to combine ECT with intra-tumoral injection of TLR9 ligands: unmethylated CpG oligodeoxynucleotides (CpG-ODN). The distant and local antitumoral effect of this association (ECT + CpG-ODN) were tested in mice bearing a tumour on the two flanks (fibrosarcoma or melanoma). Animals were treated on the left flank only by a unique ECT course followed by intratumoral injection of CpG-ODN. Tumor growth rates were monitored on both treated (left) and non-treated (right) sides in order to assess direct and systemic antitumor effects of the association respectively. Experiments were also performed on nude mice, in order to investigate the role of lymphocytes in the systemic antitumor effect. Results: Compared to the separated treatments alone we found an increased local efficacy of the ECT-CpG-ODN, but, more importantly, we demonstrated a clear systemic effect of the combination on the controlateral tumors. In nude mice, no effect was observed in controlateral tumors suggesting a mechanism mediated by T lymphocytes. No significant financial relationships to disclose.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2006.24.18_suppl.12507
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2006
detail.hit.zdb_id:
2005181-5
