Sivanandham M, Scoggin S D, Sperry R G, Wallack M K
Department of Surgery, Mount Sinai Medical Center, Miami Beach, FL.
Ann Plast Surg. 1992 Jan;28(1):114-8. doi: 10.1097/00000637-199201000-00029.
Conventional treatment of cancer, especially for patients with metastatic melanoma tumor, is often ineffective. Immunotherapy and recently introduced gene therapy have revolutionized the treatments of patients with metastatic melanoma tumor. Use of biological response modifiers, such as interleukins and interferons, have been found to enhance therapeutic benefits to patients with malignant melanoma. Initial studies with a high-dose interleukin-2 (IL-2) therapy have proved effective in patients with melanoma tumor, although a variety of systemic toxicities were observed. A low-dose IL-2 continuous infusion has shown a similar response in patients with melanoma tumor, but produced lesser toxicity. The low-dose IL-2 therapy has been studied with an adoptive transfer combined with either autologous lymphokine activated killer cells or autologous tumor infiltrating lymphocytes (TIL). IL-2 in combination with chemotherapeutic agents such as flavone acetic acid, dacarbazine, and cyclophosphamide have also been studied in patients with metastatic melanoma. Results have shown a moderate response in patients with metastatic melanoma. TIL therapy, however, has been shown to result in higher objective regression due to potent tumor-specific killing and tumor-specific targeting characters of the TIL. The tumor targeting nature of the TIL creates the possibility of using TIL as a vehicle to deliver gene product specifically to tumor tissue. Safety and toxicity of gene-transduced TIL were addressed by the use of neomycin-resistant, gene-transduced TIL in patients with metastatic melanoma. We also investigated the use of vaccinia oncolysate therapy by using the viral oncolysate prepared with IL-2 gene encoded vaccinia virus. Preliminary studies with murine hepatic metastases colon model have shown encouraging results.
癌症的传统治疗方法，尤其是对于转移性黑色素瘤患者，往往效果不佳。免疫疗法以及最近引入的基因疗法彻底改变了转移性黑色素瘤患者的治疗方式。已发现使用生物反应调节剂，如白细胞介素和干扰素，可增强对恶性黑色素瘤患者的治疗效果。高剂量白细胞介素-2（IL-2）疗法的初步研究已证明对黑色素瘤患者有效，尽管观察到了多种全身毒性。低剂量IL-2持续输注在黑色素瘤患者中显示出类似的反应，但产生的毒性较小。低剂量IL-2疗法已与过继性转移相结合进行研究，该过继性转移联合了自体淋巴因子激活的杀伤细胞或自体肿瘤浸润淋巴细胞（TIL）。IL-2与化疗药物如黄酮乙酸、达卡巴嗪和环磷酰胺联合使用也已在转移性黑色素瘤患者中进行了研究。结果显示转移性黑色素瘤患者有中度反应。然而，由于TIL具有强大的肿瘤特异性杀伤和肿瘤特异性靶向特性，TIL疗法已被证明可导致更高的客观缓解率。TIL的肿瘤靶向特性使得将TIL用作载体将基因产物特异性递送至肿瘤组织成为可能。通过在转移性黑色素瘤患者中使用抗新霉素基因转导的TIL，研究了基因转导TIL的安全性和毒性。我们还通过使用由编码IL-2基因的痘苗病毒制备的病毒溶瘤产物，研究了痘苗溶瘤产物疗法的应用。对小鼠肝转移结肠癌模型的初步研究已显示出令人鼓舞的结果。
