Enhancement of anti-tumor activity of recombinant interleukin-2 (rIL-2) by immunocomplexing with a monoclonal antibody against rIL-2.
We have investigated biological properties of an immune complex of recombinant interleukin-2 (rIL-2) and a monoclonal antibody against rIL-2 in mice for induction of killer cells and for anti-tumor activity. We have also examined the clearance of subcutaneously-injected immune complex in mice and compared it with that of rIL-2 alone. Plasma rIL-2 levels were sustained longer in mice given the immune complex than in mice given rIL-2 alone at a dose of 10 micrograms/mouse, and they were detectable even at 24 hours after the administration of the immune complex, while they fell to undetectable levels by 6 hours after the administration of rIL-2 alone. A more significant portion of rIL-2 was detected in lymph nodes after subcutaneous injection of the immune complex than that of rIL-2 alone. Splenic lymphocytes from mice given the immune complex demonstrated a higher killer cell activity against YAC-1 cells than those from mice given rIL-2 alone. The immune complex also exerted more significant anti-tumor effect in a dose-dependent manner in Meth-A fibrosarcoma-bearing mice than rIL-2 alone. Our results indicate that immunocomplexing of rIL-2 with an antibody against rIL-2 provides a useful tool as the drug delivery system for cancer therapy using rIL-2.
Sato
J
J
DDS Research Laboratories, Takeda Chemical Industries, Osaka, Japan.
Hamaguchi
N
N
Doken
K
K
Gotoh
K
K
Ootsu
K
K
Iwasa
S
S
Ogawa
Y
Y
Toguchi
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000936:Antigen-Antibody Complex / Q000276:immunology*; D000970:Antineoplastic Agents / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D000922:Immunotoxins / Q000494:pharmacology; D007376:Interleukin-2 / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D051379:Mice; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D000970:Antineoplastic Agents; D000922:Immunotoxins; D007376:Interleukin-2; D011994:Recombinant Proteins