Adoptive immunotherapy of murine pulmonary metastases with interleukin 2 and interferon-gamma.
We examined the activities of activated lymphocytes, interferon-gamma (IFN-gamma), and interleukin 2 (IL-2) in adoptive immunotherapy of pulmonary metastases. Pulmonary metastases produced in Balb/c mice by a single tail-vein injection of 5 X 10(5) murine sarcoma (MCB8) tumor cells on day 0 were treated with combinations of Con A-activated lymphocytes (CAL) (3 X 10(7) cells on days 3 and 7), IL-2 (5 X 10(4) U three times a day on days 3 to 8), and IFN-gamma (5 X 10(4) U/mouse on days 1 to 8). Treated tumors contained increased numbers of infiltrating Thy-1.2+ lymphocytes and a predominance of L3T4+(CD4+) lymphocytes. The level of expression of class I and class II MHC antigens by tumor cells in the lung was increased after treatment. Mice that received CAL + IL-2 + IFN-gamma showed approximately 80% reduction in tumor burden as compared to controls (P = 0.001). Mice treated with IL-2 + CAL, or IL-2 + IFN-gamma, displayed approximately 50% reduction (both P less than 0.02 as compared to triple therapy), whereas IL-2, IFN-gamma, or CAL administered as single agents had little effect on pulmonary metastases. We conclude that adoptive immunotherapy with activated lymphocytes and IL-2 is enhanced by IFN-gamma.
Dubinett
S M
SM
Department of Medicine, Massachusetts General Hospital, Boston, MA 02114.
Kurnick
J T
JT
Kradin
R L
RL
D000818:Animals; D005260:Female; D007116:Immunization, Passive; D007371:Interferon-gamma / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D008223:Lymphoma / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D012513:Sarcoma, Experimental / Q000276:immunology / Q000473:pathology; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma