Quinn T J, Healy N, Sara A, Maggi E, Claros C S, Kabarriti R, Scandiuzzi L, Liu L, Gorecka J, Adem A, Basu I, Yuan Z, Guha C
Department of Radiation Oncology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
Department of Surgery, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY, USA.
Cancer Gene Ther. 2017 Jan;24(1):13-19. doi: 10.1038/cgt.2016.70. Epub 2016 Dec 9.
The incidence of melanoma in the United States continues to rise, with metastatic lesions notoriously recalcitrant to therapy. There are limited effective treatment options available and a great need for more effective therapies that can be rapidly integrated in the clinic. In this study, we demonstrate that the combination of RGD-targeted adeno-associated virus phage (RGD-AAVP-TNF) with hypofractionated radiation therapy results in synergistic inhibition of primary syngeneic B16 melanoma in a C57 mouse model. Furthermore, this combination appeared to modify the tumor microenvironment, resulting in decreased Tregs in the draining LN and increased tumor-associated macrophages within the primary tumor. Finally, there appeared to be a reduction in metastatic potential and a prolongation of overall survival in the combined treatment group. These results indicate the use of targeted TNF gene therapy vector with radiation treatment could be a valuable treatment option for patients with metastatic melanoma.
美国黑色素瘤的发病率持续上升，转移性病变对治疗 notoriously 难治。目前有效的治疗选择有限，迫切需要能够迅速应用于临床的更有效疗法。在本研究中，我们证明了RGD靶向腺相关病毒噬菌体（RGD-AAVP-TNF）与低分割放射治疗相结合，可在C57小鼠模型中协同抑制原发性同基因B16黑色素瘤。此外，这种联合治疗似乎改变了肿瘤微环境，导致引流淋巴结中的调节性T细胞减少，原发性肿瘤内的肿瘤相关巨噬细胞增加。最后，联合治疗组的转移潜能似乎有所降低，总生存期有所延长。这些结果表明，靶向TNF基因治疗载体与放射治疗联合应用可能是转移性黑色素瘤患者的一种有价值的治疗选择。
