Electroporation improves the anti-tumour efficacy of chemotherapeutic and gene therapies. Combining electroporation-mediated chemotherapeutics with interleukin 12 (IL-12) plasmid DNA produces a strong yet safe anti-tumour effect for treating primary and refractory tumours. A previously published report demonstrated the efficacy of a single cycle of IL-12 plasmid DNA and bleomycin in canines, and, similarly, this study further demonstrates the safety and efficacy of repeated cycles of chemotherapy plus IL-12 gene therapy for long-term management of aggressive tumours. Thirteen canine patients were enrolled in this study and received multiple cycles of electro-chemo-gene therapy (ECGT) with IL-12 pDNA and either bleomycin or gemcitabine. ECGT treatments are very effective for inducing tumour regression via an antitumour immune response in all tested histotypes except for sarcomas, and these treatments can quickly eradicate or debulk large squamous cell carcinomas. The versatility of ECGT allows for response-based modifications which can overcome treatment resistance for affecting refractory lesions. Importantly, not a single severe adverse event was noted even in animals receiving the highest doses of chemotherapeutics and IL12 pDNA over multiple treatment cycles. This report highlights the safety, efficacy and versatility of this treatment strategy. The data reveal the importance of inducing a strong anti-tumour response for successfully affecting not only the treated tumours, but also non-treated metastatic tumours. ECGT with IL12 pDNA plus chemotherapy is an effective strategy for treating multiple types of spontaneous cancers including large, refractory and multiple tumour burdens.

The ability to control the immune system to actively attack tumors would be a marvelous weapon to combat the incessant attack of cancer. Unfortunately, safe and effective methods are not yet available. To overcome the impediments to this control, tumor-targeted (tt) Interleukin (IL) 12 plasmid DNA can be safely delivered to accessible tumors, and these treatments can induce antitumor immune responses in both the treated and untreated tumors. Here, electroporation-mediated ttIL12 pDNA treatments are shown to be safe and well tolerated in a dose escalation study in canines bearing naturally-occurring neoplasms. The final patient received treatment with up to 3,800 μg pDNA distributed throughout five separate squamous cell carcinoma tumors, doses equivalent to those administered in a Phase I trial with wildtype IL12 pDNA. Not a single severe adverse event occurred in any patient at any of the five dose levels, and only minor, transient changes were noted in any tested parameter. Clinical response analysis and immune marker mRNA detection of treated and non-treated lesions confirmed that the ttIL12 pDNA treatments in only a few tumors could elicit antitumor immune responses in the treated lesions as well as distant metastatic lesions. These observations and results prove that ttIL12 pDNA can be safely administered at clinical levels, and these treatments can effect both treated and non-treated, metastatic lesions.

This prospective experimental simulation study evaluated the efficiency, ease of use (EOU) and cost of administering chemotherapy with two closed system transfer devices (CSTD, Equashield™ and PhaSeal ) and no CSTD. Forty-six veterinary technicians (VT) working in oncology specialty practices were timed during chemotherapy administration simulated with water and a model canine limb 10 times with each system and with no CSTD. EOU and likelihood of recommending each system were rated by VT using visual analog scales. Costs were obtained from veterinary distributors. Administration was fastest with Equashield™ (P = 0.0003), but the difference was not enough to affect case flow. Equashield™ was easier to use than PhaSeal or no CSTD (P = 0.002), however VT recommended both CSTD more strongly than no CSTD (P < 0.0001). Equashield™ cost less than PhaSeal but was sold only in bulk quantities. CSTD did not decrease efficiency in administering chemotherapy and were readily accepted by VT.