Potent tumoricidal effects of a human cytotoxic T-cell line (TALL-104) against prostate cancer

Abstract

The human TALL-104 cell line possesses major histocompatibility complex non-restricted cytotoxic activity against a large variety of tumor targets. Adequate therapies for prostate cancer that has spread outside its capsule are lacking. In order to identify effective therapies for this problem, we investigated the antiproliferative effects of TALL-104 cells against three prostate cancer cell lines (LNCaP, PC-3, DU-145). A Cr-51-release: cytotoxicity assay showed that TALL-104 cells were very cytotoxic against the prostate cancer cells. For example, at a 1:1 ratio of TALL-104 cells to prostate cancer cells, the percent release of Cr-51 at 18 h were 50, 40, and 45% for LNCaP, PC-3, and DU-145, respectively. Analysis by inhibition of clonogenic growth of prostate cancer cells also showed that TALL-104 cells were extremely effective. For instance, a short-term (4 h or 18 h) pre-incubation of TALL-104 cells with these tumor cells at the effector to target ratio of 10:1 prior to clonogenic assay resulted in a substantial reduction in clonogenic tumor growth (90%, 65%, and 50% clonal growth inhibition for LNCaP, PC-3, and DU-145, respectively). Further experiments using both Cr-51 release and clonogenic assays showed that irradiated TALL-104 cells were also effective in their anti-prostatic cancer activities. We also examined if TALL-104 cells plus a chemotherapeutic agent might complement each other in their cytotoxic effects. Preincubation of prostate cancer cell targets with etoposide (0.2-20 mu g/ml) for 18 h markedly increased their susceptibility to TALL-104 lysis. The anti-tumor efficacy of TALL-104 cells was also demonstrated in vivo utilizing the BNX murine model engrafted with subcutaneous PC-3 prostate cancer cells. A substantial reduction in PC-3 tumor cell progression was observed in mice injected with irradiated TALL-104 cells (1x10(7) cells intraperitoneally or intratumorally for 5 days beginning on days 24 and 45 after implantation) as compared to mice injected with tumors only. Taken together, these findings suggest that TALL-104 cells may be utilized as a potent anti-tumor agent, either alone or in combination with other agents (such as etoposide) in metastatic prostate cancer.