Publications
Department of Medicine faculty members published more than 3,600 peer-reviewed articles in 2024.
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PURPOSE
Gene-based immunotherapy for cancer is limited by the lack of safe, efficient, reproducible, and titratable delivery methods. Direct injection of DNA into tissue, although safer than viral vectors, suffers from low gene transfer efficiency. In vivo electroporation, in preclinical models, significantly enhances gene transfer efficiency while retaining the safety advantages of plasmid DNA.
PATIENTS AND METHODS
A phase I dose escalation trial of plasmid interleukin (IL)-12 electroporation was carried out in patients with metastatic melanoma. Patients received electroporation on days 1, 5, and 8 during a single 39-day cycle, into metastatic melanoma lesions with six 100-mus pulses at a 1,300-V/cm electric field through a penetrating six-electrode array immediately after DNA injection. Pre- and post-treatment biopsies were obtained at defined time points for detailed histologic evaluation and determination of IL-12 protein levels.
RESULTS
Twenty-four patients were treated at seven dose levels, with minimal systemic toxicity. Transient pain after electroporation was the major adverse effect. Post-treatment biopsies showed plasmid dose proportional increases in IL-12 protein levels as well as marked tumor necrosis and lymphocytic infiltrate. Two (10%) of 19 patients with nonelectroporated distant lesions and no other systemic therapy showed complete regression of all metastases, whereas eight additional patients (42%) showed disease stabilization or partial response.
CONCLUSION
This report describes the first human trial, to our knowledge, of gene transfer utilizing in vivo DNA electroporation. The results indicated this modality to be safe, effective, reproducible, and titratable.
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BACKGROUND
The Mexico-U.S. border region is experiencing rising rates of blood-borne infections among injection drug users (IDUs), emphasizing the need for harm reduction interventions.
METHODS
We assessed the religious and cultural factors affecting the acceptability and feasibility of three harm reduction interventions--Needle exchange programs (NEPs), syringe vending machines, and safer injection facilities (SIFs)--in Tijuana, Mexico. In-depth qualitative interviews were conducted with 40 community stakeholders to explore cultural and societal-related themes.
RESULTS
Themes that emerged included Tijuana's location as a border city, family values, and culture as a mediator of social stigma and empathy towards IDUs. Perception of low levels of both awareness and socio-cultural readiness for harm reduction interventions was noted. Religious culture emerged as a theme, highlighting the important role religious leaders play in determining community responses to harm reduction and rehabilitation strategies for IDUs. The influence of religious culture on stakeholders' opinions concerning harm reduction interventions was evidenced by discussions of family and social values, stigma, and resulting policies.
CONCLUSION
Religion and politics were described as both a perceived benefit and deterrent, highlighting the need to further explore the overall influences of culture on the acceptability and implementation of harm reduction programs for drug users.
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