Soluble glucan and lymphokine-activated killer (LAK) cells in the therapy of experimental hepatic metastases.
Previous studies have indicated the efficacy of adoptive immunotherapy utilizing recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells in the treatment of advanced neoplastic disease. However, this therapeutic approach is associated with considerable toxicity, primarily due to the systemic administration of rIL-2. The present study was undertaken to determine the efficacy of a newly developed water-soluble glucan, when administered in combination with LAK cells, in the therapy of experimental hepatic metastases. Mice were challenged subcutaneously (1 X 10(4) cells) with reticulum cell sarcoma M5076 on day 0. Therapy was initiated on day 15, when a palpable primary tumor mass and hepatic micrometastases were evident, and continued at 3-day intervals up to day 54. Sarcoma-bearing mice received glucan (250 mg/kg) intravenously, either alone or in combination with LAK cells (1 X 10(7)/mouse). Control mice received 5% (wt/vol) dextrose in water. Glucan-LAK cell therapy significantly suppressed primary tumor growth, inhibited the progression of hepatic metastases and prolonged survival in sarcoma-bearing mice. Splenocytes, incubated with rIL-2 for 72 h, exhibited significant natural killer (NK) cell activity and were cytotoxic to sarcoma cells in vitro. Glucan-LAK cell administration resulted in significant increases in splenic NK cell activity and Kupffer cell-mediated tumoricidal activity. In addition, bone marrow proliferation was enhanced following the co-administration of glucan and LAK cells. Due to its nontoxic nature and immunostimulating properties, soluble glucan may prove to be an attractive biological response modifying agent for utilization in adoptive immunotherapy of advanced neoplastic disease.
Sherwood
E R
ER
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana 70112.
Williams
D L
DL
McNamee
R B
RB
Jones
E L
EL
Browder
I W
IW
Di Luzio
N R
NR
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D005936:Glucans / Q000627:therapeutic use*; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000637:transplantation; D007728:Kupffer Cells / Q000276:immunology; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000276:immunology / Q000556:secondary / Q000628:therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology; D014185:Transplantation, Isogeneic
D005936:Glucans; D007376:Interleukin-2