[Induction of T cell responses against autologous ovarian cancer by anti-idiotype minibody-pulsed dendritic cells]

Abstract

Background & objective: Immunotherapy of sensitizing dendritic cells (DCs) with antigen,protein,and frozen cancer cell has been widely used in treating various cancers. The 6B11 anti-idiotype-antibody,a fusion protein prepared by our research center,can mimic ovarian cancer-associated antigen OC166-9. This study was to induce T cell cytotoxicity against autologous tumor cells of patients with ovarian cancer by 6B11 anti-idiotype-antibody.

Methods: Peripheral blood samples were collected from 10 patients with epithelial ovarian cancer,Monocytes were isolated and cultured to obtain DCs. Immature DCs were stimulated with 6B11 anti-idiotype-antibody (MINI-DC group); unpulsed DCs (unpulsed-DC group),mouse F(ab) '2 fragments pulsed DCs [F(ab)'2-DC group],and T cells alone (T group) were served as controls. Mature DCs were harvested. (3)H-thymidine ((3)H-TdR) incorporation approach was used to measure effect of DCs on stimulating auto-T cell proliferation. Cytotoxicity of DC-activated T cells against auto-tumor cells was measured with (51)Cr 6-h release test,tumor cell lines,SKOV3,HLE,and K562, were used as controls.

Results: In 4 cases,cpm value of (3)H-TdR incorporation,as symbol of auto-T cell proliferation, in MINI-DC group was significantly higher than those in control groups. In 5 cases,specific cytotoxicity effect of T cells on auto-tumor cells was observed in MINI-DC group at effect-target ratio of 20:1,the toxicity effect of T cells in MINI-DC group was 25%-100%,significantly higher than those in F(ab)'2-DC group (18%-40%), unpulsed-DC group (13%-43%),and T group (9%-58%). In 4 cases,the toxicity effect of T cells in MINI-DC group, at effect-target ratio of 20:1,on auto-tumor cells was 25%-100%, higher than those on SKOV3 cells (5%-51%),HLE cells (2%-38%),and K562 cells (2%-25%). Moreover,the toxicity effect of T cells in MINI-DC group on auto-tumor cells can be partially blocked by anti-MHC-I antibody,which indicated that the toxicity was antigen-specific.

Conclusion: DCs loaded with 6B11 anti-idiotype antibody that mimic ovarian cancer antigen can induce antigen specific T cell cytotoxicity against auto-ovarian tumor cells in vitro.