Cytotoxic effects of T cells induced by fusion protein 6B11-pulsed dendritic cells on ovarian carcinoma cells.
BACKGROUND
6B11 anti-idiotype minibody, a fusion protein, has been shown to mimic ovarian carcinoma associated antigen OC166-9. This study was designed to determine whether 6B11 anti-idiotype minibody-pulsed dendritic cells (DCs) can induce cytotoxic T cells against ovarian cancer cells.


METHODS
Monocytes were isolated from peripheral blood mononuclear cells collected from patients with epithelial ovarian carcinoma (n=10). The monocytes-derived immature DCs were stimulated by cytokines, and mature DCs were pulsed with 6B11 anti-idiotype-minibody or murine F(ab)'2 fragments. The proliferation of autologous T cells induced by DCs was determined by 3H-thymidine uptake. The cytotoxicity of DC-activated T cells against autologous carcinoma cells was determined by 51Cr-release assay.


RESULTS
Purified T cells demonstrated strong proliferation following incubation with 6B11 anti-idiotype minibody-pulsed DCs in 4 of 10 patients. The specific cytotoxicity of purified T cells against autologous carcinoma cells was induced after stimulation with 6B11 anti-idiotype minibody-pulsed DCs in 5 of 10 patients with cytotoxic effects ranging from 25 to 95%. In contrast, isotype murine F(ab)'2 fragments-pulsed DCs did not induce T cell proliferation and cytotoxicity against the targets. Additionally, the cytotoxic effect was partially inhibited by anti-MHC class-I antibody indicating that the cytotoxic effects are antigen-specific.


CONCLUSIONS
6B11 anti-idiotype-antibody-pulsed DCs can induce T cell proliferation and T cell-mediated cytotoxicity against autologous ovarian tumor cells in vitro. The cytotoxic effects of T cells against autologous tumor cells are antigen-specific. These data implicate the rationale for the use of 6B11 anti-idiotype minibody as immunotherapy against ovarian carcinoma.
Yang
Wenlan
W
Gynecologic Oncology Center, People's Hospital, Peking University, Beijing, 100044, PR China.
Feng
Jie
J
Chang
Xiaohong
X
Fu
Tianyun
T
Ye
Xue
X
Zhang
Hong
H
Li
Xiaoping
X
Wen
Hongwu
H
Feng
Limin
L
Tong
Chunrong
C
Cui
Heng
H
D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology / Q000494:pharmacology*; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D002291:Carcinoma, Papillary / Q000276:immunology / Q000628:therapy; D018284:Cystadenocarcinoma, Serous / Q000276:immunology / Q000628:therapy; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006801:Humans; D007128:Immunoglobulin Fragments / Q000276:immunology / Q000494:pharmacology; D016219:Immunotherapy, Adoptive / Q000379:methods*; D008213:Lymphocyte Activation; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D007128:Immunoglobulin Fragments; D011993:Recombinant Fusion Proteins