Inhibition of murine Lewis lung carcinoma metastases by combined chemotherapy and intranasal THF-gamma 2 immunotherapy.

Abstract

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.

• Authors: G Rashid, R Ophir, M Pecht, S Lourie, A Meshorer, S Ben-Efraim, N Trainin, Y Burstein, Y Keisari
• Journal: Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy (J Immunother Emphasis Tumor Immunol) Vol. 19 Issue 5 Pg. 324-33 (Sep 1996) ISSN: 1067-5582 [Print] United States
• PMID: 8941872 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Oligopeptides
• Thymus Hormones
• thymic humoral factor gamma 2
• Melphalan
• Fluorouracil

Topics

• Adjuvants, Immunologic (therapeutic use)
• Administration, Intranasal
• Animals
• Carcinoma, Lewis Lung (pathology, secondary, therapy)
• Combined Modality Therapy
• Female
• Fluorouracil (therapeutic use)
• Immunotherapy, Active
• Lung (drug effects, pathology)
• Lung Neoplasms (pathology, secondary, therapy)
• Male
• Melphalan (therapeutic use)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Oligopeptides (administration & dosage, therapeutic use)
• Organ Size (drug effects)
• Spleen (cytology)
• Survival Analysis
• T-Lymphocyte Subsets (cytology)
• Thymus Hormones (therapeutic use)