Electrochemotherapy of tumors as in situ vaccination boosted by immunogene electrotransfer

G. SERSA; J. TEISSIE; M. CEMAZAR; E. SIGNORI; G. MARSHALL

Cancer Immunology and Immunotherapy

Spriger

Lugar: Berlin; Año: 2015 vol. 1 p. 1 - 20

Electroporation is a platform technology fordrug and gene delivery. When applied to cell in vitro or tissuesin vivo, it leads to an increase in membrane permeabilityfor molecules which otherwise cannot enter the cell(e.g., siRNA, plasmid DNA, and some chemotherapeuticdrugs). The therapeutic effectiveness of delivered chemotherapeuticsor nucleic acids depends greatly on their successfuland efficient delivery to the target tissue. Therefore,the understanding of different principles of drug and gene delivery is necessary and needs to be taken into accountaccording to the specificity of their delivery to tumors and/or normal tissues. Based on the current knowledge, electrochemotherapy(a combination of drug and electric pulses)is used for tumor treatment and has shown great potential.Its local effectiveness is up to 80 % of local tumor control,however, without noticeable effect on metastases. Inan attempt to increase systemic antitumor effectiveness ofelectrochemotherapy, electrotransfer of genes with immunomodulatoryeffect (immunogene electrotransfer) couldbe used as adjuvant treatment. Since electrochemotherapycan induce immunogenic cell death, adjuvant immunogeneelectrotransfer to peritumoral tissue could lead tolocoregional effect as well as the abscopal effect on distantuntreated metastases. Therefore, we propose a combinationof electrochemotherapy with peritumoral IL-12 electrotransfer,as a proof of principle, using electrochemotherapyboosted with immunogene electrotransfer as in situ vaccinationfor successful tumor treatment.