Antitumor effect of an antibody against gastrointestinal cancer-associated antigen CA19.9.
Despite tremendous efforts in developing cancer vaccines and monoclonal antibodies (mAbs), only a few passive or active immunotherapeutic modalities have succeeded. The failure may be due to the existence of immunosuppressive factors, which caused anergy of patients' immune system. In this study, we discovered that CA19.9 is one such immunosuppressive factor, which could inhibit the proliferation of activated human lymphocytes. However, this inhibition could be reversed by a mAb, LC44, which was specifically generated against CA19.9. An in vitro cytotoxic experiment showed that mAb LC44 could form an immunocomplex with CA19.9, which subsequently induced the production of cytotoxic T-cells reacting to CA19.9-positive cancer cells. In addition, mAb LC44 could mediate the complement-dependent cytotoxicity to CA19.9-positive cancer cells. mAb LC44 showed an antitumor effect in immunodeficient mice with colon cancer burden in the presence or absence of CA19.9. Based on the observations from this study, we postulated that the mAb, LC44, could be a promising antitumor agent for gastrointestinal cancer and worthy of further investigation.
Li
Zheng
Z
State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, PUMC, Beijing, China.
Liu
Xueli
X
Wan
Yunxia
Y
Wang
Wei
W
Ma
Jie
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D018395:CA-19-9 Antigen / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005770:Gastrointestinal Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007116:Immunization, Passive / Q000379:methods*; D053208:Kaplan-Meier Estimate; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
D000911:Antibodies, Monoclonal; D018395:CA-19-9 Antigen