title: Tolerability of two sequential electroporation treatments using MedPulser DNA delivery system (DDS) in healthy adults.
abstract: Immunotherapy against infectious agents and malignant tumors requires efficient priming of effector cells through direct expression and/or efficient cross-presentation of antigens by antigen-presenting cells. Electroporation is a new procedure aimed at transiently increasing cell membrane permeability and direct delivery of antigen or antigen-encoding nucleic acids inside targeted cells. We evaluated the tolerability including compliance with repeated electroporation treatments using MedPulser DDS in 24 healthy adults. Pain severity was evaluated at time of electroporation treatment, and at 1, 5, 10, and 20 minutes, and 24 hours thereafter, using two clinically validated questionnaires: McGill Pain Questionnaire (MPQ) (Present Pain Intensity) and Brief Pain Inventory (BPI). Electroporation treatments were generally well tolerated. Twenty-two out of 24 subjects returned for the second electroporation treatment 14 days after first treatment. Only two subjects reported a treatment-related systemic adverse experience following either electroporation application. For both pain assessment tools, maximum pain and/or discomfort were mostly reported immediately (within 5 minutes) after electroporation; Furthermore, no difference was observed when comparing peak-pain scores after first and second electroporation treatments. This study supports the clinical application of MedPulser DDS for the improvement of antigen-induced immune responses for prophylactic or therapeutic vaccines, especially in gene-based therapies for cancer.
authors.affiliation: Department of Anesthesiology, University of California San Diego, San Diego, California, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Wallace
authors.forename: Barbara
authors.initials: B
authors.lastname: Evans
authors.forename: Sandra
authors.initials: S
authors.lastname: Woods
authors.forename: Robin
authors.initials: R
authors.lastname: Mogg
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Adam C
authors.initials: AC
authors.lastname: Finnefrock
authors.forename: Dietmar
authors.initials: D
authors.lastname: Rabussay
authors.forename: Michael
authors.initials: M
authors.lastname: Fons
authors.forename: John
authors.initials: J
authors.lastname: Mallee
authors.forename: Devan
authors.initials: D
authors.lastname: Mehrotra
authors.forename: Florian
authors.initials: F
authors.lastname: Schödel
authors.forename: Luwy
authors.initials: L
authors.lastname: Musey
mesh_terms: D000293:Adolescent; D000328:Adult; D018274:Electroporation / Q000295:instrumentation* / Q000379:methods; D005260:Female; D015316:Genetic Therapy / Q000295:instrumentation* / Q000379:methods*; D006801:Humans; D007167:Immunotherapy; D008297:Male; D010147:Pain Measurement; D055815:Young Adult