Efficacy and specificity of a monoclonal antibody-drug conjugate in chemotherapy by intratumoral injection.
The murine monoclonal antibody (Mab) A7 conjugated to neocarzinostatin (A7-NCS) was injected intratumorally (IT) into tumor bearing nude mice. Its pharmacokinetics and tumoricidal effects were compared in the high, moderate and low antigen expressing xenograft for SW1116, WiDr and KB tumor-bearing nude mice, respectively. When injected IT into nude mice, [125I]A7-NCS was retained in the tumors according to the degree of antigen expression; it was also disseminated into the blood inverse proportion to the antigen expression. Addition of an excess amount of Mab A7 reduced [125I]-A7-NCS accumulation in SW1116 xenograft and elevated the [125I]A7-NCS concentration in the circulation. Complete tumor reduction was found in all 5 mice with SW1116 tumor, and 2 of 5 mice with WiDr tumor. However, only incomplete tumor suppression was observed in mice with the KB tumor. The significant tumor reduction in SW1116 bearing nude mice was attenuated when excess of Mab A7 was simultaneously administered with A7-NCS. These findings indicate that A7-NCS was localized in the target tumors and exerted its tumoricidal effects depending on the degree of antigen-antibody interaction when administered IT. Thus, A7-NCS can be used successfully in vivo for local therapy, auguring new and promising applications for local cancer therapy.
Kitamura
K
K
First Department of Surgery, Kyoto Prefectural University of Medicine.
Takahashi
T
T
Miyagaki
T
T
Yamaoka
N
N
Tsurumi
H
H
Ohtsuji
E
E
Kamiguchi
M
M
Noguchi
A
A
Yamaguchi
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000918:Antibody Specificity; D000951:Antigens, Neoplasm / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000922:Immunotoxins / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D015552:Injections, Intralesional; D007457:Iodine Radioisotopes; D007624:KB Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011863:Radioimmunoassay; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D009353:Zinostatin / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D009353:Zinostatin