[Antitumor effect of IL-2 entrapped in liposomes on rat hepatoma, AH-66].
The human recombinant interleukin 2 (IL-2) was entrapped in liposomes, and the therapeutic effects of the liposomes containing IL-2 (Lip-IL-2) were experimentally studied using the rat hepatoma strain, AH-66, maintained in donryu rats and challenged subcutaneously in the inguinal region. The peri-tumor injections of Lip-IL-2 (15 X 10(4)/kg units for the IL-2 dose) significantly inhibited the tumor growth as determined from the relative mean tumor weight, although no therapeutic effects were observed when the unentrapped IL-2 or liposomes containing saline was administered rats in the same way as the injections of Lip-IL-2. They also prolonged the survival time of rats. The studies of serum IL-2 values after i.v. or s.c. injections of Lip-IL-2 revealed that IL-2 was released gradually from the liposomes containing IL-2 into the circulation. As the result of the tumor tissue staining of the immunoperoxidase 18 hrs after the peri-tumor injection of IL-2, it was shown that a number of macrophages infiltrated into the tumor tissue and degenerated tumor cells were observed adjacent to those macrophages. It is suggested that Lip-IL-2 is useful as an antineoplastic agent in the immunotherapy and that the therapeutic effects of Lip-IL-2 would be related to both the slow release of IL-2 and the cytotoxicity on the tumor cells mediated by the macrophages.
Konno
H
H
2nd Dept. of Surgery, Hamamatsu University.
Toriyama
H
H
Aoki
K
K
Baba
S
S
Sakaguchi
S
S
Yamashita
A
A
Tadakuma
T
T
D000818:Animals; D004337:Drug Carriers; D004341:Drug Evaluation; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008081:Liposomes; D008114:Liver Neoplasms, Experimental / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008264:Macrophages / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use
D004337:Drug Carriers; D007376:Interleukin-2; D008081:Liposomes; D011994:Recombinant Proteins