Immunotherapy with the immunomodulating
thymic humoral factor-gamma 2 (THF-gamma 2) octapeptide, combined with
1,3-bis(2-chloroethyl)-1-nitrosourea (
BCNU)
chemotherapy, will be used for enhancing host immune response to arrest pulmonary
metastases of a B16-F10.9
melanoma tumor. In this experimental model of pulmonary
metastasis, the highly metastatic B16-F10.9
melanoma tumor cells (2 x 10(5)) were inoculated into the footpad of mice to form a primary
tumor. The
tumor-bearing leg was surgically removed on reaching the size of 5.5 mm, which resulted in the appearance of
metastases in the lungs of the animals. After
tumor excision, mice were treated intraperitoneally with a single dose of
BCNU (20 or 35 mg/kg) followed by a series of intraperitoneal THF-gamma 2
injections (1 microgram/0.5 ml/injection). Relative to untreated mice and those receiving
chemotherapy alone, the antitumor action of the combined THF-gamma 2 chemoimmunotherapy protocol was significantly augmented according to the following in vivo parameters: (a) decreased postsurgical spontaneous metastatic burden; (b) prolonged survival time; (c) increased resistance to
tumor cell challenge; and (d) massive infiltration of lymphocytes, polymorphonuclear cells, and macrophages in the lung tissue. The THF-gamma 2
immunotherapy also prevented a decrease in lymphocyte reactivity, otherwise induced by the
tumor/
BCNU chemotherapy. THF-gamma 2
immunotherapy resulted in restoration of the response to
Lipopolysaccharide mitogenic stimulation and the allogeneic response. Our data suggest that postoperative THF-gamma 2
immunotherapy could be a valuable adjunct to anticancer
chemotherapy as a treatment for metastatic arrest of
melanoma tumor.