Immunotherapeutic pre-clinical protocols in 3D models of cancer diseases and in veterinary medicine (cats and dogs affected by spontaneous malignant tumors): delivery by electroporation of engineered plasmid vectors carrying antigens/immunostimulatory DNA sequences; Target therapy by pulsed electric fields for the delivery of pharmacological molecules (Bleomycin/Cisplatin).
The use of electric pulses as a safe tool to deliver therapeutic molecules to tissues and organs has been rapidly developed over the last decades. This technology leads to a transient increase in the permeability of cell membranes when exposed to electric field pulses. This process is commonly known as electropermeabilization or electroporation.
3D cultures, thanks to the capacity of reproducing the tumor architecture, represent a more reliable model to optimize electrotransfer protocols in the aim to minimize tissue injury and enhance transfection efficiency.
Histological images of HCC1954 (A) and MDA-MB231 (B) cells cultured in the 3D scaffold for seven days. Representative images acquired by an inverted microscope after staining with Hematoxylin and Eosin (H&E), Masson Trichrome (MT), and Wiegert Van Gieson (WVG) methods. The blue arrows indicate cells, the white stars the extracellular matrix, and the white arrows indicate collagen. Cancers 2020, 12, 1043
Gene electrotransfer (GET) by plasmid DNA carrying sequences of antigens and/or immunostimulatory molecules, such as Interleukins, not only allows the enhancement of DNA in-take and an improvement of DNA synthesis. It also acts as adjuvant for the stimulation of both Innate and Adaptive Immunity. The therapeutic gene can be administered either intratumorally or peritumorally for predominantly local effectiveness, or into the muscle to induce systemic shedding of the therapeutic molecule.
Recent Patents on Anti-Infective Drug Discovery, 2008, 3, 93-101
Electrochemotherapy (ECT) is used for the delivery of chemotherapeutic drugs, such as bleomycin or cisplatin, to tumors. It has reached wide clinical acceptance. The treatment induces local immune response and immunogenic cell death.
Immunogenic effects of ElectrochemotherapyUrska Kamensek, Spela Kos, and Gregor Sersa. Adjuvant Immunotherapy as a Tool to Boost Effectiveness of Electrochemotherapy.Handbook of Electroporation, 2016
Gene Electrotransfer by pDNAs coding for immunomodulatory molecules such as cytokines, chemokines, and/or administration of DNA vaccines carrying tumor-specific or tumor associate antigens can be used in combination with Electrochemotherapy for tumor treatments.
Pet animals are a very translational model, since they develop spontaneous tumors. ECT in combination with GET using plasmids coding canine IL-2 and IL-12 in dogs affected by spontaneous inoperable stage III–IV canine oral malignant melanoma could represent a good anti- tumor strategy.
On the left, the patient with malignant melanoma located in the palate (white arrow) on the day of the ECT+GET treatment. On the right, 90 days after the treatment: a complete response was obtained. Vaccines 2023, 11, 1033