Cytotoxic effects of T cells induced by fusion protein 6B11-pulsed dendritic cells on ovarian carcinoma cells

Autor: Xue Ye, Heng Cui, Tian-Yun Fu, Hong Zhang, Xiaohong Chang, Xiaoping Li, Li-Min Feng, Jie Feng, Hong-Wu Wen, Chun-Rong Tong, Wen-Lan Yang
Rok vydání: 2007
Předmět:
Zdroj: Gynecologic Oncology. 105:238-243
ISSN: 0090-8258
DOI: 10.1016/j.ygyno.2006.04.028
Popis: Introduction 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 3 H-thymidine uptake. The cytotoxicity of DC-activated T cells against autologous carcinoma cells was determined by 51 Cr-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. Conclusion 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.
Databáze: OpenAIRE