Effects of recombinant alpha-interferon-gelatin conjugate on in vivo murine tumor cell growth.
A recombinant human alpha-interferon A/D (IFN), also known to be effective in mice, was conjugated to gelatin with a water-soluble carbodiimide. The IFN-gelatin conjugate was much more efficient than free IFN in activating mouse peritoneal macrophages (Mø) in an in vitro experiment to inhibit the growth of IFN-resistant subline cells (RR1) of murine fibrosarcoma. A single i.p. injection of the conjugate administered to normal mice was also more effective than one of free IFN in activating peritoneal Mø and natural killer cells in peritoneal exudate cell and spleen cell populations. In the investigation on body distribution of the IFN-gelatin conjugate, an enhanced affinity to Mø as well as a prolonged retention were observed in comparison with free IFN. An injection of the IFN-gelatin conjugate i.p. was more effective than one of free IFN in suppressing the in vivo growth of not only IFN-sensitive SS2 cells but also RR1 cells in the peritoneal cavity of mice, although RR1 cells were only susceptible to the indirect effect of IFN via host cells, in contrast to SS2 cells. In addition to an increased recruitment of Mø to the peritoneal cavity in RR1-bearing mice receiving i.p. injection of the IFN-gelatin conjugate, these Mø were activated to inhibit the in vitro growth of RR1 cells. These results indicate that the IFN-gelatin conjugate is a promising antitumor agent that is much more effective than free IFN. The dose of IFN in the conjugate required for exerting the antitumor effects is much lower than that of free IFN, which leads to a reduction of adverse effects of IFN.
Tabata
Y
Y
Research Center for Biomedical Engineering, Kyoto University, Japan.
Uno
K
K
Yamaoka
T
T
Ikada
Y
Y
Muramatsu
S
S
D000818:Animals; D004306:Dose-Response Relationship, Immunologic; D004337:Drug Carriers; D005260:Female; D005354:Fibrosarcoma / Q000378:metabolism / Q000628:therapy*; D005780:Gelatin / Q000493:pharmacokinetics / Q000494:pharmacology*; D007370:Interferon Type I / Q000493:pharmacokinetics / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010534:Peritoneal Neoplasms / Q000276:immunology; D011994:Recombinant Proteins; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
D004337:Drug Carriers; D007370:Interferon Type I; D011994:Recombinant Proteins; D005780:Gelatin