Unidad de Transferencia Genética, Instituto de Oncología "Ángel H. Roffo", Universidad de Buenos Aires, Buenos Aires, Argentina.
Gene Ther. 2019 Nov;26(10-11):418-431. doi: 10.1038/s41434-019-0066-7. Epub 2019 Mar 11.
After 6 years of follow-up treating 364 canine melanoma patients, we present here results about the proof-of-concept, safety, and efficacy of a new surgery adjuvant combined gene therapy. The adjuvant treatment (AT) group was divided in three arms as follows: (i) complete surgery plus vaccine (CS-V), (ii) complete surgery plus combined treatment (CS-CT), and (iii) partial surgery plus combined treatment (PS-CT). Besides the genetic vaccines composed by tumor extracts and lipoplexes carrying human interleukin-2 and granulocyte-macrophage colony-stimulating factor genes, the patients were subjected to combined treatment received in the post-surgical bed injections of lipid-complexed thymidine kinase suicide gene plus ganciclovir and canine interferon-β gene plus bleomycin. As compared with surgery-only treated controls (So), CS-CT and CS-V treatments significantly increased the fraction of local disease-free (from 20 to 89 and 74%) and distant metastases-free patients (M0: from 45 to 87 and 84%). Although less effective than CS arms, PS-CT arm demonstrated a significantly improved control of metastatic disease (M0: 80%) compared with So (M0: 44%). In addition, AT produced a significant 9.3- (CS-CT), 6.5- (CS-V), and 5.4-fold (PS-CT) increase of overall survival as compared with their respective So controls. In general terms, the AT changed a lethal disease into a chronic disease where 70% of CS-CT, 51% of CS-V, and 14% of PS-CT patients died of melanoma unrelated causes. These surgery adjuvant treatments delayed or prevented post-surgical recurrence and distant metastasis, and improved disease-free and overall survival while maintaining quality of life. These successful outcomes encourage assaying a similar scheme for human melanoma.
在对 364 例犬黑色素瘤患者进行了 6 年的随访后，我们在此报告了一种新的手术辅助联合基因治疗的概念验证、安全性和疗效的结果。辅助治疗（AT）组分为以下三个分支：（i）完全手术加疫苗（CS-V），（ii）完全手术加联合治疗（CS-CT），和（iii）部分手术加联合治疗（PS-CT）。除了由肿瘤提取物和携带人白细胞介素-2 和粒细胞-巨噬细胞集落刺激因子基因的脂质体组成的基因疫苗外，患者还接受了术后床注射脂质复合物胸苷激酶自杀基因加更昔洛韦和犬干扰素-β基因加博来霉素的联合治疗。与仅接受手术治疗的对照组（So）相比，CS-CT 和 CS-V 治疗显著增加了局部无病（从 20%增加到 89%和 74%）和无远处转移（M0：从 45%增加到 87%和 84%）的患者比例。尽管不如 CS 组有效，但 PS-CT 组与 So 相比，对转移性疾病的控制明显改善（M0：80%对 44%）。此外，与各自的 So 对照组相比，AT 使总生存显著增加了 9.3 倍（CS-CT）、6.5 倍（CS-V）和 5.4 倍（PS-CT）。一般来说，AT 将一种致命疾病转变为一种慢性疾病，其中 70%的 CS-CT、51%的 CS-V 和 14%的 PS-CT 患者死于与黑色素瘤无关的原因。这些手术辅助治疗延迟或预防了术后复发和远处转移，并提高了无病和总生存，同时保持了生活质量。这些成功的结果鼓励对人类黑色素瘤进行类似的方案检测。
