可控基因传递能够增强黑素瘤免疫治疗效果

Title:Controlled Gene Delivery Can Enhance Therapeutic Outcome for Cancer Immune Therapy for Melanoma

Volume: 15 Issue: 1

Author(s): Shawna A. Shirley, Cathryn G. Lundberg, Fanying Li, Niculina Burcus and Richard Heller

Affiliation:

关键词: 细胞因子，电转，基因治疗，免疫疗法，白介素-12，黑素瘤

摘要: Effective delivery still remains a major hurdle in the development of gene based therapies. While technological advances have occurred that have improved delivery in general, there is still a need for controlled delivery in order to achieve therapeutic effects. Gene electrotransfer (GET) can be utilized to accomplish this. Careful selection of parameters used for delivery such as amplitude, duration and number of pulses as well as plasmid construct can be manipulated in order to achieve appropriate levels of local expression. Previously we have shown that direct delivery of the therapeutic cytokine, interleukin 12 (IL-12), to tumors using electrotransfer can generate local and systemic anti-tumor effects in pre-clinical and clinical studies. Using this model we hypothesized that modulating local gene expression using GET can affect therapeutic outcome. To test this, we used multiple GET protocols and plasmids to achieve varying levels of local IL-12 expression. We found that high local gene expression did not give rise to a better therapeutic outcome. This suggests the level and possibly the duration of gene expression are important in mediating the host immune response against melanoma. These data also emphasize the importance of considering the desired immune outcome of the therapy when selecting parameters for GET.

Cite this article as:

Shawna A. Shirley, Cathryn G. Lundberg, Fanying Li, Niculina Burcus and Richard Heller , Controlled Gene Delivery Can Enhance Therapeutic Outcome for Cancer Immune Therapy for Melanoma, Current Gene Therapy 2015; 15 (1) . https://dx.doi.org/10.2174/1566523214666141121111630