Freedman R.S., Bowen J.M., Delcos L., Edwards C.L., Wallace S., Atkinson E.N., Ioannides C.G., Kasi L.P., Scott W., Patenia R.
Departments of Gynecology, Tumor Biology, Clinical Radiotherapy, Diagnostic Radiology, Nuclear Medicine and Biomathematics, The University of Texas M.D. Anderson Cancer Center, Texas, USA.
Int J Gynecol Cancer. 1994 Mar;4(2):101-110. doi: 10.1046/j.1525-1438.1994.04020101.x.
A pilot clinical trial was conducted in patients with squamous carcinoma of the uterine cervix to evaluate the clinical and biologic effects of active intralymphatic immunotherapy (AILI) with allogenic viral oncolysate (VO) prior to radiation therapy. Sixteen patients with advanced primary squamous carcinoma of the uterine cervix and lymph node metastases underwent bipedal intralymphatic injections of VO. VO was derived from lysates of cervical carcinoma cells that had been infected with influenza A virus. AILI was repeated after 2 weeks and followed one week later by standard or extended-field radiation therapy (RT). The first seven patients were treated at one of the three dose levels: 6 mg (three patients), 12 mg (three patients) and 18 mg (one patient). Remaining patients were treated at the 12 mg dose level. Sixteen patients received 63 injections (one patient received three of four doses) of AILI-VO without significant toxicity. Eleven patients have died of persistent or recurrent carcinoma with a total median survival of 19.4 months. Examination of humoral and cellular immunity during AILI-VO showed an increase in the serum liters of antibodies to a surface antigen on cervical carcinoma cells and to the influenza virus. Increased non-MHC restricted lymphocyte cytotoxicity was exhibited by three of four patients treated above the first dose level. Two of the three patients are survivors. By contrast, lymphocytes of patients treated with AILI-VO exhibited either an increase or a decrease in proliferation responses to cervical carcinoma cells. Similarly, post-treatment lymphocytes exhibited either helper or suppressor inducer effects on pre-treatment lymphocytes.
在子宫颈鳞状细胞癌患者中进行了一项试点临床试验，以评估放疗前采用同种异体病毒溶瘤产物（VO）进行主动淋巴内免疫疗法（AILI）的临床和生物学效应。16例患有晚期原发性子宫颈鳞状细胞癌并伴有淋巴结转移的患者接受了VO双足淋巴内注射。VO源自感染甲型流感病毒的宫颈癌细胞裂解物。2周后重复进行AILI，1周后进行标准或扩大野放射治疗（RT）。前7例患者接受了三种剂量水平之一的治疗：6mg（3例患者）、12mg（3例患者）和18mg（1例患者）。其余患者接受12mg剂量水平的治疗。16例患者接受了63次AILI-VO注射（1例患者接受了四剂中的三剂），无明显毒性。11例患者死于持续性或复发性癌症，总中位生存期为19.4个月。在AILI-VO期间对体液和细胞免疫进行检查发现，血清中针对宫颈癌细胞表面抗原和流感病毒的抗体升。在高于第一剂量水平治疗的4例患者中，有3例表现出非MHC限制淋巴细胞细胞毒性增加。这3例患者中有2例存活。相比之下，接受AILI-VO治疗的患者淋巴细胞对宫颈癌细胞的增殖反应要么增加，要么减少。同样，治疗后的淋巴细胞对治疗前的淋巴细胞表现出辅助或抑制诱导作用。
