IL-12 plasmid delivery by in vivo electroporation for the successful treatment of established subcutaneous B16.F10 melanoma
IL-12 plasmid delivery by in vivo electroporation for the successful treatment of established subcutaneous B16.F10 melanoma
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DOI：
10.1006/mthe.2002.0601
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发表时间：
2002-06-01
影响因子：
12.4
通讯作者：
Heller, R
中科院分区：
文献类型：
--
作者：
Lucas, ML;Heller, L;Heller, R
白介素12(IL-12)已被用于多种针对黑色素瘤的免疫治疗方案。然而，IL-12以重组蛋白的形式传递会导致严重的毒性，基因治疗对B16.F10小鼠黑色素瘤的成功有限。本研究旨在探讨体内电穿孔转导IL-12基因作为抗B16.F10黑色素瘤药物的有效性。我们用瘤内注射(I.T.)治疗荷B16.F10黑色素瘤的小鼠。或肌肉内(I.M.)注射编码IL-12的质粒，然后体内电穿孔。对于IT。为了治疗，我们使用了一个包含六个穿透电极的敷贴器，以提供1500-V/cm，100-mus的脉冲。我们给他注射了肌注。使用包含四个穿透电极的涂布器提供100-V/cm、20-ms脉冲。IT部门。治疗使47%的荷瘤小鼠治愈，70%的治愈小鼠对B16.F10细胞的攻击具有抵抗力。IM。治疗并没有导致肿瘤的消退。我们发现了那个IT。治疗后肿瘤内IL-12和干扰素-γ水平升高，淋巴细胞流入肿瘤，血管减少。两人都不是IM。也不是IT。在裸鼠模型中，对B16.F10肿瘤的治疗是成功的，支持T细胞在该肿瘤模型的消退中的作用。
Interleukin-12 (IL-12) has been used in numerous immunotherapy protocols against melanoma. However, delivery of IL-12 in the form of recombinant protein can result in severe toxicity, and gene therapy has had limited success against B16.F10 murine melanoma. The purpose of this study was to examine the effectiveness of in vivo electroporation for the delivery of plasmid DNA encoding IL-12 as an antitumor agent against B16.F10 melanoma. We treated mice bearing established B16.F10 melanoma tumors with intratumoral (i.t.) or intramuscular (i.m.) injections of a plasmid encoding IL-12, followed by in vivo electroporation. For i.t. treatments, we used an applicator containing six penetrating electrodes to deliver 1500-V/cm, 100-mus pulses. We administered i.m. pulses with an applicator containing four penetrating electrodes delivering 100-V/cm, 20-ms pulses. The i.t. treatment resulted in the cure of 47% of tumor-bearing mice, and 70% of cured mice were resistant to challenge with B16.F10 cells. The i.m. treatment did not result in tumor regression. We found that i.t. treatment resulted in increased levels of IL-12 and interferon-gamma (IFN-gamma) within the tumors, the influx of lymphocytes into the tumors, and reduction in vascularity. Neither i.m. nor i.t. treatment was successful against B16.F10 tumors in a nude mouse model, supporting a role for T cells in regression of this tumor model.