ウサギＶＸ２舌癌におけるフィブロネクチンによるＯＫ‐４３２の抗腫よう効果増強に関する研究

Abstract

Activation of antigen specific T cells requires not only antigen-recognizing signals obtained via T-cell receptors (TCR) but also co-stimulatory signals produced by contact with antigen-presenting cells. Furthermore, without costimulatory signals, clonal anergy develops even if T cells make contact with TCR. Recent studies have shown that these signals are induced by fibronectin (FN), which comprises one type of extracellular matrix. We therefore evaluated the use of FN for immunotherapy in the rabbit VX 2 tongue cancer model. FN was administered concomitantly with OK-432 (OK), a biological response modifier, to the area around the cancer.Enhancement of the anticancer effect of OK by FN was investigated with respect to invasion by the transplanted cancer, deep cervical lymph node metastasis, and number of T cells infiltrating into the cancer.1) The OK+FN group showed significantly better suppression of the cancer growth rate than did the control group (P<0.05) and the OK group (P<0.05).2) The OK group and the OK+FN group showed significantly better suppression of deep cervical lymph node metastasis than did the control group (P<0.025, P<0.025), but there was no significant difference between the OK group and the OK +FN group.3) The OK+FN group showed a significantly higher number of T-cells infiltrating into the cancer than did the control group (P<0.001) and the OK group (P<0.01).4) Fibrosis of the cancer stroma and increasing number of infiltrating T-cells apparently enhanced the anticancer effect of OK with FN.These results suggest that FN enhances the anticancer effect of OK and therefore may be useful for immunotherapy in the future.