Immunotherapy by a slow delivery system of interleukin-2 in mice models.
A sustained release system for interleukin-2 (IL-2), and IL-2 mini-pellet (IL-2 mp), was developed by fusing IL-2 into a needle shaped collagen. Serum concentration of IL-2 after a single subcutaneous injection of the IL-2 mp into C57BL/6 mice remained elevated longer than after an injection of aqueous IL-2. IL-2 in the serum became undetectable by 6h after a subcutaneous injection of 1 x 10(6) unit of IL-2 in phosphate-buffered saline (PBS). In contrast, after a single subcutaneous injection of IL-2 mp containing the same amount of IL-2, the concentration of IL-2 increased to its maximum at 6h after injection, then began to decrease gradually. IL-2 was detected even on the third day after a single subcutaneous injection of one IL-2 mp. Augmentation of NK activity and generation of IL-2 activated killer cells were observed in the spleen from day 1--day 3 after a single subcutaneous injection of IL-2 mp into C57BL/6 mice. This activation was not observed following a single subcutaneous injection of the same amount of IL-2 in PBS. Adoptive immunotherapy by a single subcutaneous injection of IL-2 mp followed by intravenous injections of in vitro cultured IL-2 activated killer cells showed better results in decreasing the number of metastases of Lewis lung carcinoma in C57BL/6 mice than immunotherapy using IL-2 solution.(ABSTRACT TRUNCATED AT 250 WORDS)
Okayama Central Hospital, Japan.
J
J
Matsuoka
K
K
Sakagami
T
T
Fujiwara
T
T
Onoda
H
H
Idani
A
A
Gochi
K
K
Orita
D000818:Animals; D003692:Delayed-Action Preparations; D004195:Disease Models, Animal; D004343:Drug Implants / Q000493:pharmacokinetics*; D005260:Female; D016219:Immunotherapy, Adoptive / Q000379:methods*; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000378:metabolism / Q000556:secondary / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000276:immunology
D003692:Delayed-Action Preparations; D004343:Drug Implants; D007376:Interleukin-2