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

Abstract

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 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.

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.