Thymic humoral factor-gamma 2 (THF-gamma 2) immunotherapy reduces the metastatic load and restores immunocompetence in 3LL tumor-bearing mice receiving anticancer chemotherapy.
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.
Ophir
R
R
Department of Human Microbiology, Sackler Faculty of Medicine, Tel Aviv University, Israel.
Pecht
M
M
Keisari
Y
Y
Rashid
G
G
Lourie
S
S
Meshorer
A
A
Ben-Efraim
S
S
Trainin
N
N
Burstein
Y
Y
D000818:Animals; D004357:Drug Synergism; D064420:Drug-Related Side Effects and Adverse Reactions; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000187:drug effects; D007106:Immune Sera / Q000276:immunology; D007109:Immunity / Q000187:drug effects*; D007167:Immunotherapy / Q000379:methods*; D008070:Lipopolysaccharides / Q000276:immunology; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy; D008297:Male; D008558:Melphalan / Q000009:adverse effects / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000401:mortality / Q000628:therapy*; D009842:Oligopeptides / Q000627:therapeutic use*; D013951:Thymus Hormones / Q000627:therapeutic use*
D007106:Immune Sera; D008070:Lipopolysaccharides; D009842:Oligopeptides; D013951:Thymus Hormones; C064563:thymic humoral factor gamma 2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008558:Melphalan; D005472:Fluorouracil