18 Further studies of these agents in prostate cancer treatment are ongoing. Tumor Cell Vaccines Rather than administering single or multiple antigens

to target an antitumor reaction, tumor vaccines use autogenic or allogenic tumor cells to generate an immune response. Such vaccines stimulate multiple antigens, potentially minimizing the ability of the tumor cells to evade detection. Before Inhibitors,research,lifescience,medical their use in prostate cancer, tumor cell vaccines were investigated in renal cell carcinoma, lung cancer, and melanoma. Typically adjuvants are used with the tumor vaccine to stimulate the immune response to break tolerance to tumor antigens. An early trial involved the use of autologous tumor cells taken at the time of radical prostatectomy.19 The cells were then expanded ex vivo, transfected with GM-CSF complementary DNA, lethally irradiated, and administered intradermally. Cells were evaluated for GM-CSF secretion and DNA integration before injection. Inhibitors,research,lifescience,medical Eleven patients with advanced prostate cancer had cells harvested. Eight of these patients had successful primary cultures and were eligible for Inhibitors,research,lifescience,medical analysis. The majority of patients had temporary irritation at the injection site, with occasional click here low-grade fevers and malaise. Two of the 8 patients

had delayed-type hypersensitivity before therapy, whereas 7 had delayed-type hypersensitivity during and after therapy, indicating induction of a T-cell response to tumor antigens. Three patients developed new antibodies to tumor cell antigens, indicating a B-cell response as well. The investigators concluded that this approach was feasible and safe, though 3 of 11 subjects were unable to participate owing to difficulties with cell expansion. Subsequent trials using tumor cell vaccines transfected with GM-CSF have

Inhibitors,research,lifescience,medical been performed using allogenic prostate cancer cell lines, namely LnCaP and PC3 cells. This Inhibitors,research,lifescience,medical has been developed as the GVAX® vaccine for prostate cancer (Cell Genesys, South San Francisco, CA). For this vaccine, each cell line is transfected with GM-CSF, irradiated, and examined for GM-CSF production and DNA integration as with the autologous study described above. Simons and others20 described the first phase I/II trial with the GVAX vaccine in 21 men with biochemical recurrence within over 4 years of radical prostatectomy. Patients received weekly injections of the vaccine (6 × 107 cells from each cell line) for 8 weeks with minimal side effects. The injection sites were found on histopathology to have invasion of inflammatory cells and APCs. Sixteen of 21 patients had decreasing PSA velocities at 5 months (P < .001), and 1 patient had a greater than 50% PSA reduction for 7 months. In a second phase II trial of GVAX,21 55 men with HRPC (34 with asymptomatic metastasis, 21 with no detectable metastasis) were treated with a 500 × 106-cell priming dose and either a 100 × 106-cell (low-dose) or 300 × 106-cell (high-dose) boost every 2 weeks for 6 months.