Abstract

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.