SBIR-STTR Award

The contents of this proposal are based on the observation that, both in vitro and in vivo, the cytotoxicity of some anticancer drugs can be greatly increased if cells are transiently permeabilized, allowing easier passage of the drug, by application of short and intense pulsed electric fields. The objectives and specific aims of this current proposal are to extend the data we have already obtained on tumor regression in animal models with murine melanoma cell lines, by combining bleomycin with electric field. In particular, we will (i) compare different routes of administration, intratumor and intravenous, and investigate the effect of (ii) different dosages, and (iii) multiple treatments, all with bleomycin and optimized electrical parameters. Results of the combination therapy will be compared with three sets of control, namely, no drug and no electric field, and drug or electric field alone. Apart from usual monitoring and observation of the animals, detailed histopathological examinations will also be carried out. In addition, field plots with different geometry of the electrodes, caliper and needles, will be obtained. The long-term aim of the project is to treat human patients with skin cancers, particularly advanced melanoma and basal cell carcinoma by this novel method. PROPOSED COMMERCIAL APPLICATION: The technology will allow treatment of cancer patients using existing anticancer drugs with maximum efficacy. Electroporation-mediated chemotherapy has shown great promise in phase I/II clinical trial of patients with head and neck squamous cell carcinomas.

Thesaurus Terms:
bleomycin, drug delivery system, melanoma, method development, neoplasm /cancer chemotherapy, nonhuman therapy evaluation disease model, drug administration rate /duration, drug administration route, drug adverse effect electric field, electroporation, laboratory mouse

The long term objective of this program is the development of effective therapies for treatment of solid malignant tumors. Electrochemotherapy (ECT) combines electroporation with very low doses of antitumor agents and has been shown to enhance the effectiveness of drugs. This phase II proposal will continue the systematic development of ECT that was initiated in Phase I. The focus will be on the following specific aims: (i) examine the distribution of the electric field in and around the tumor, (ii) determine if ECT can be used to enhance the effectiveness of several antitumor agents, (iii) optimization of electroporation parameters for in vivo animal studies with different drugs, (iv) continue the limited but highly encouraging clinical study to test this delivery system using the newly developed needle array, (v) develop instrumentation that will be sued in the treatment of caner patients. The completion of these aims will lead to the development of instruments for use in laboratory animals and in humans. The latter will be finished a the end of Phase II and will be suitable for treating skin cancer in humans in Phase III.Proposed commercial application:Permeabilizing a tumor cell membrane permits rapid uptake of a chemotherapeutic agent and enhances cytoxicity. This research will develop in year 1 hardware suitable for use by the research community for treating malignant tumors on small animals; year 2 work will finalize hardware for use in patients. Attractive features will include greater drug efficacy and an absence of systemic side effects due to local delivery of very low drug dosage.Thesaurus termsbiomedical equipment development, drug delivery system, electrochemistry, electron radiation, electroporation, neoplasm /cancer chemotherapy antineoplastic, basal cell carcinoma, clinical biomedical equipment, cytotoxicity, electrode cell line, clinical research, histology, human subject, laboratory mouseNational Cancer Institute (NCI)