thymic-humoral-factor-gamma-2 and Plasmacytoma

We reported previously that treatment of mice bearing MOPC-315 plasmacytoma with the drugs L-PAM (phenylalanine mustard) or 5-FU (5-fluorouracil), in combination with low doses of THF-gamma 2, was more effective in increasing their survival time than treatment with the drug alone. We show here that in the combined treatment using a single injection of 5-FU followed by multiple (8-15) injections of THF-gamma 2, the megadoses were more effective than the low doses in increasing the survival time of MOPC-315 tumor-bearing mice. On the other hand, in combination with L-PAM, both low and high doses of THF-gamma 2 were equally effective. The need for high doses of THF-gamma 2, when used in combination with 5-FU, could be due to the fact that 5-FU acts as a "non-immunomodulating" drug and has to be used at a high, immunosuppressive dose.

Topics: Animals; Cell Line; Combined Modality Therapy; Dose-Response Relationship, Drug; Fluorouracil; Immunotherapy; Melphalan; Mice; Mice, Inbred BALB C; Oligopeptides; Plasmacytoma; Thymus Hormones

BALB/c mice cured of large MOPC-315 plasmacytomas by melphalan remain deficient in their spleen T-cell functions. This was manifested by impairment of the allogeneic and the antibody responses in vitro to SRBC and in decreased numbers of T-cells including their subsets CD4 and CD8. IL-2 production and specific cytotoxicity against MOPC-315 tumor cells were, on the other hand, maintained. Treatment of these cured mice by in-vivo administration of THF-gamma 2, an octapeptide from calf thymus, repaired these deficits. This was evidenced by in vitro tests with spleen cells which manifested an increased allogeneic response and elevated generation of primary antibody response, restoration of T-cell subpopulations to normal and an enhanced IL-2 production above normal levels. The potential use of THF-gamma 2 as supportive therapy in cancer treatment is suggested.

Topics: Animals; Cytotoxicity Tests, Immunologic; Drug Evaluation, Preclinical; Erythrocytes; Flow Cytometry; Fluorescent Antibody Technique; Immunologic Deficiency Syndromes; Interleukin-2; Lymphocyte Culture Test, Mixed; Male; Melphalan; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neoplasm Transplantation; Oligopeptides; Plasmacytoma; Spleen; Thymus Hormones

The effect of a synthetic thymic hormone, THF-gamma 2, on the anti-tumor activity of spleen cells was studied in mice immunized against the RPC-5 tumor. Following two courses of the THF-gamma 2 treatment, the mean RPC-5 specific cytotoxic response of immune spleen cells was significantly increased when compared to normal cells (P less than 0.001) and to untreated immune spleen cells (P less than 0.04). In addition, THF-gamma 2 treatment improved the competence of immune spleen cells in adoptive immunotherapy (AIT) when performed in combination with chemotherapy by melphalan. Recipients of spleen cells from THF-gamma 2 treated mice showed a 35% increase in survival when compared to AIT with immune cells alone. The results suggest that THF-gamma 2 treatment of donors for AIT might be applicable to cancer therapy in humans.

Topics: Animals; Combined Modality Therapy; Cytotoxicity, Immunologic; Immunotherapy; Male; Melphalan; Mice; Mice, Inbred BALB C; Oligopeptides; Plasmacytoma; Spleen; Thymus Hormones