thymic-humoral-factor-gamma-2 and Lung-Neoplasms

In mice bearing immunogenic tumors, adding thymic humoral factor-gamma 2 (THF-gamma 2)1 immunotherapy as an adjunct to anticancer chemotherapeutic regimens not only potentiates the antitumor activity of each drug but also repairs tumor/chemotherapy-induced damage to T-cell populations and functions. The Lewis lung carcinoma (3LL) is a weakly immunogenic, highly metastatic tumor in C57BL/6 mice. To investigate whether the immunoregulatory octapeptide is also effective against a tumor that does not elicit an antitumor immune response, we assessed the effect of combination THF-gamma 2 immunotherapy and chemotherapy in 3LL-bearing mice. The results indicate that THF-gamma 2 combined with either Melphalan or 5-Fluorouracil was more effective in reducing metastatic load than either chemotherapeutic drug alone and was characterized by massive infiltration of lymphatic cells. The combined chemoimmunotherapy treatment also prolonged the survival time in all treated animals and repaired T-cell defects and impaired in vitro cellular immune response parameters, induced either by the tumor or by chemotherapy. THF-gamma 2 immunotherapy reversed the decrease in the number of bone-marrow myeloid colonies (GM-CFU) induced by chemotherapy treatment of tumor-bearing mice, supporting the hypothesis that THF-gamma 2 directly stimulates the proliferation of myeloid stem cells. The overall results imply, that when administered as an adjunct to chemotherapy, THF-gamma 2 immunotherapy is equally effective against immunogenic and nonimmunogenic tumors.

Topics: Animals; Drug Synergism; Drug-Related Side Effects and Adverse Reactions; Erythrocytes; Female; Fluorouracil; Granulocyte-Macrophage Colony-Stimulating Factor; Immune Sera; Immunity; Immunotherapy; Lipopolysaccharides; Lung Neoplasms; Male; Melphalan; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Metastasis; Neoplasms, Experimental; Oligopeptides; Thymus Hormones

Previous research in our laboratories has shown that the immunoregulatory octapeptide, THF-gamma 2, potentiates the efficacy of anticancer chemotherapy in experimental animal models of local plasmacytoma and repairs drug-induced defects in immunocompetence. The highly metastatic, murine D122 lung carcinoma model has been shown to be useful for evaluating the efficacy of experimental antimetastatic therapeutic modalities. The goal of the present study was to determine whether intranasal thymic humoral factor-gamma 2 (THF-gamma 2) immunotherapy, after a single dose of chemotherapy, could inhibit the development of lung metastases, restore immunocompetence, and increase survival in syngeneic C57BL/6 mice bearing highly metastatic Lewis lung carcinoma (D122) solid footpad tumors. Relative to untreated mice and those receiving chemotherapy alone, mice receiving combined chemoimmunotherapy showed the following significant differences: (a) decreased lung metastatic load as assessed by lung weight, (b) prolonged survival time, (c) massive infiltration of lymphoid cells in the lungs, and (d) restoration of impaired immune parameters to normal values in melphalan-treated mice. THF-gamma 2 prevented tumor emboli from colonizing the target tissue, probably by inducing expansion of the lymphoid cell compartment. When used as an adjunct to anticancer chemotherapy, intranasal THF-gamma 2 immunotherapy is a simple and safe treatment modality that seems to be promising for inhibiting lung metastases.

Topics: Adjuvants, Immunologic; Administration, Intranasal; Animals; Carcinoma, Lewis Lung; Combined Modality Therapy; Female; Fluorouracil; Immunotherapy, Active; Lung; Lung Neoplasms; Male; Melphalan; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Oligopeptides; Organ Size; Spleen; Survival Analysis; T-Lymphocyte Subsets; Thymus Hormones