Tumor destruction using electrochemotherapy followed by CpG oligodeoxynucleotide injection induces distant tumor responses.

Roux S, Bernat C, Al-Sakere B, Ghiringhelli F, Opolon P, Carpentier AF, Zitvogel L, Mir LM, Robert C.
Cancer Immunol Immunother. 2008 Sep;57(9):1291-300. Epub 2008 Feb 8.

PURPOSE: Electrochemotherapy (ECT) is an effective local therapy of human cutaneous cancers but has no effect on distant untreated tumors. We addressed whether tumor-associated antigens released after ECT could induce an efficient systemic immunity when associated with an appropriate immunoadjuvant. METHODS AND RESULTS: We first studied the nature of the cellular recruitment and the expression of various toll-like receptors (TLRs) in tumors treated by ECT. We found that ECT induced a massive recruitment of CD11c and CD11b positive cells in the tumors and a strong increase of TLR9 expression. We then tested antitumor effects of the combination: ECT followed by TLR-9 ligands, CpG oligodeoxynucleotides (CpG ODN), in three murine tumor models. We found that this combination triggered both potent local synergistic antitumor effects, on the ipsi-lateral ECT-treated tumor, and more interestingly, a systemic antitumor response on the contra-lateral untreated tumor, in the three models. The systemic protection was T-cell dependent as it was not observed in nude littermates. The combination induced tumor-specific T cell effectors in the tumor-draining lymph nodes and in the spleen which secreted significantly more gamma-interferon upon activation than with ECT or CpG ODN alone. CONCLUSIONS: Our data show that ECT and CpG ODN synergize and induce a significant increase of the local effect and a systemic T-dependent antitumor response. Such combination constitutes a potential innovative vaccination strategy using in situ tumor-associated antigens that could eventually be translated into the clinic.

URL: http://www.springerlink.com/content/c21m382283x16272/

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/18259749

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