Antibody-dependent cytotoxicity mediated by chimeric monoclonal antibody Nd2 and experimental immunotherapy for pancreatic cancer.
In a previous study, mouse monoclonal antibody (MoAb) Nd2 (m-Nd2, mouse IgG1) labeled with (131)I exhibited efficacy in in vivo radioimmunotherapy against pancreatic cancer. In this study we prepared mouse / human chimeric antibody Nd2 (c-Nd2, human IgG1) for clinical use and examined whether c-Nd2 induced antibody-dependent cell-mediated cytotoxicity (ADCC). Cytotoxicity to pancreatic cancer (PC) cell lines, including Nd2 antigen-positive (SW1990, RWP-1, Capan-1) and Nd2 antigen-negative (Panc-1, MiaPaca-2, Capan-2) lines, was evaluated by mixed human leukocyte and tumor cell culture (MLTC) at an effector cell to target cell (E / T) ratio of 50 with or without Nd2. Cytotoxicities to SW1990 with no antibody, m-Nd2 and c-Nd2 (1 microg / ml) were 26.7%, 38.0% and 55%, respectively; to RWP-1, 28%, 41% and 70%; to Capan-1, 26%, 30% and 52%; to Panc-1, 24%, 28% and 30%; to MiaPaca-2, 18%, 20% and 27% and to Capan-2, 29. 7%, 35.0% and 40.6%. Cytotoxic capacity during MLTC with c-Nd2 was significantly higher than during MLTC with m-Nd2 or with no antibody. These findings indicated that cytotoxicity to Nd2-positive PC cells during MLTC is induced by ADCC. Intraperitoneal injection of c-Nd2 inhibited the tumor growth of SW1990 xenografted subcutaneously in nude mice and prolonged the survival of nude mice in which SW1990 tumor was transplanted orthotopically at the tail of the pancreas. These findings suggested that, because of its ability to induce ADCC, c-Nd2 may be clinically useful for the immunotherapeutic treatment of pancreatic cancer.
Nishihara
T
T
First Department of Surgery, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan. m1355299@med.osaka-cu.ac.jp
Sawada
T
T
Yamamoto
A
A
Yamashita
Y
Y
Ho
J J
JJ
Kim
Y S
YS
Chung
K H
KH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000915:Antibody Affinity; D000920:Antibody-Dependent Cell Cytotoxicity; D004195:Disease Models, Animal; D006801:Humans; D007167:Immunotherapy; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D011993:Recombinant Fusion Proteins