THF-gamma 2-mediated reduction of pulmonary metastases and augmentation ofimmunocompetence in C57BL/6 mice bearing B16-melanoma

Immunotherapy with the immunomodulating thymic humoral factor-gamma 2 (THF- gamma 2) octapeptide, combined with 1,3-bis(2-chloroethyl)-1-nitrosourea (B CNU) chemotherapy, will be used for enhancing host immune response to arres t pulmonary metastases of a B16-F10.9 melanoma tumor. In this experimental model of pulmonary metastasis, the highly metastatic B16-F10.9 melanoma tum or cells (2 x 10(5)) were inoculated into the footpad of mice to form a pri mary tumor. The tumor-bearing leg was surgically removed on reaching the si ze of 5.5 mm, which resulted in the appearance of metastases in the lungs o f the animals. After tumor excision, mice were treated intraperitoneally wi th a single dose of BCNU (20 or 35 mg/kg) followed by a series of intraperi toneal THF-gamma 2 injections (1 mu g/0.5 ml/injection). Relative to untrea ted mice and those receiving chemotherapy alone, the antitumor action of th e combined THF-gamma 2 chemoimmunotherapy protocol was significantly augmen ted according to the following in vivo parameters: (a) decreased postsurgic al spontaneous metastatic burden; (b) prolonged survival time; (c) increase d resistance to tumor cell challenge; and (d) massive infiltration of lymph ocytes, polymorphonuclear cells, and macrophages in the lung tissue. The TH F-gamma 2 immunotherapy also prevented a decrease in lymphocyte reactivity, otherwise induced by the tumor/BCNU chemotherapy. THF-gamma 2 immunotherap y resulted in restoration of the response to Lipopolysaccharide mitogenic s timulation and the allogeneic response. Our data suggest that postoperative THF-gamma 2 immunotherapy could be a valuable adjunct to anticancer chemot herapy as a treatment for metastatic arrest of melanoma tumor.