INHIBITION OF MURINE LEWIS LUNG-CARCINOMA METASTASES BY COMBINED CHEMOTHERAPY AND INTRANASAL THF-GAMMA-2 IMMUNOTHERAPY

Previous research in our laboratories has shown that the immunoregulat ion octapeptide, THF-gamma 2, potentiates the efficacy of anticancer c hemotherapy in experimental animal models of local plasmacytoma and re pairs drug-induced defects in immunocompetence. The highly metastatic, murine D122 lung carcinoma model has been shown to be useful for eval uating the efficacy of experimental antimetastatic therapeutic modalit ies. The goal of the present study was to determine whether intranasal thymic humoral factor-gamma 2 (THF-gamma 2) immunotherapy, after a si ngle dose of chemotherapy, could inhibit the development of lung metas tases, rei;tore immunocompetence, and increase survival in syngeneic C 57BL/6 mice bearing highly metastatic Lewis lung carcinoma (D122) soli d footpad tumors. Relative to untreated mice and those receiving chemo therapy alone, mice receiving combined chemoimmunotherapy showed the f ollowing significant differences: (a) decreased lung metastatic load a s assessed by lung weight, (b) prolonged survival time, (c) massive in filtration of lymphoid cells in the lungs, and (d) restoration of impa ired immune parameters to normal values in melphalan-treated mice. THF -gamma 2 prevented tumor emboli from colonizing the target tissue, pro bably by inducing expansion of the lymphoid cell compartment. When use d as an adjunct to anticancer chemotherapy, intranasal THF-gamma 2 imm unotherapy is a simple and safe treatment modality that seems to be pr omising for inhibiting metastases.