In vivoEffects of Vaccination with Six-Transmembrane Epithelial Antigen of the Prostate: A Candidate Antigen for Treating Prostate Cancer

Abstract

Immunotherapy may provide an alternative treatment for cancer patients, especially when tumors overexpress antigens that can be recognized by immune cells. The identification of markers and therapeutic targets that are up-regulated in prostate cancer has been important to design new potential treatments for prostate cancer. Among them, the recently identified six-transmembrane epithelial antigen of the prostate (STEAP) is considered attractive due to its overexpression in human prostate cancer tissues. Our study constitutes the first assessment of the in vivo effectiveness of STEAP-based vaccination in prophylactic and therapeutic mouse models. Two delivery systems, cDNA delivered by gene gun and Venezuelan equine encephalitis virus-like replicon particles (VRP), both encoding mouse STEAP (mSTEAP) and three vaccination strategies were used. Our results show that mSTEAP-based vaccination was able to induce a specific CD8 T-cell response against a newly defined mSTEAP epitope that prolonged the overall survival rate in tumor-challenged mice very significantly. This was achieved without any development of autoimmunity. Surprisingly, CD4 T cells that produced IFN;, tumor necrosis factor-A (TNF-A), and interleukin-2 (IL-2) played the main role in tumor rejection in our model as shown by using CD4-and CD8-deficient mice. In addition, the presence of high IL-12 levels in the tumor environment was associated with a favorable antitumor response. Finally, the therapeutic effect of STEAP vaccination was also assessed and induced a modest but significant delay in growth of established, 31 day old tumors. Taken together, our data suggest that vaccination against mSTEAP is a viable option to delay tumor growth. [Cancer Res 2007;67(3):1344-51]

PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses

“…C57BL/6 mice were purchased from Jackson Laboratory (Bar Harbor, ME). 1: 27-35, AAGIGILTV; 22 gp100: 154-162, KTWGQYWQV; 23 gp100: 209-217, ITDQVPFSV; 24 ovalbumin (OVA): 256-264, SIIN-FEKL, 25 and mouse six-transmembrane epithelial antigen of the prostate (mSTEAP): 326-335, DVSKINRTEM 26 ) in 1 mL of chloroform was emulsified in 6 mL of 2% PVA to form an oil-in-water emulsion. The emulsification was carried out using a micro-tip probe ultrasonic sonicator set at 55 watts of energy output (XL 2015 Sonicator ® ultrasonic processor; Misonix, Inc, Farmingdale, NY) for 2 minutes over an ice bath.…”

Concurrent Allorecognition Has a Limited Impact on Posttransplant Vaccination

“…To investigate whether alloreactivity could either promote or suppress T cell responses against self-Ags against which only lowaffinity T cells would be available, HSCT-transplanted male mice received either an mDLI or an fpDLI and a vaccine composed of male or female DC, respectively, pulsed with a peptide derived from the six-transmembrane epithelial Ag of the prostate (STEAP), found in human and prostate cancer, and previously used in vaccination strategies (37,38). Results depicted in Fig.…”

Adenovirus-mediated gene transfer of interleukin-23 shows prophylactic but not therapeutic antitumor effects

“…However, this differential efficacy of the cancer vaccine in prophylaxis and therapy has been proven by several other studies evaluating the feasibility of a cancer vaccine with tolerized tumor antigens. [42][43][44][45][46] Novakovic et al 44 found that the proportion of protected mice was 75-100% by vaccination of irradiated melanoma tumor cells with CpG ODN in a prophylactic setting whereas the rates of cured mice were only 11.1-21.1% in a therapeutic setting. Garcia-Hernandez Mde et al 45 recently reported that prophylactic vaccination with a prostate antigen, six-transmembrane epithelial antigen of prostate, significantly delayed tumor growth and improved survival whereas therapeutic vaccination induced a modest delay in the growth of established prostate tumors.…”

“…[42][43][44][45][46] Novakovic et al 44 found that the proportion of protected mice was 75-100% by vaccination of irradiated melanoma tumor cells with CpG ODN in a prophylactic setting whereas the rates of cured mice were only 11.1-21.1% in a therapeutic setting. Garcia-Hernandez Mde et al 45 recently reported that prophylactic vaccination with a prostate antigen, six-transmembrane epithelial antigen of prostate, significantly delayed tumor growth and improved survival whereas therapeutic vaccination induced a modest delay in the growth of established prostate tumors. Moreover, in a HER-2/neu transgenic mouse model which closely mimics the natural history of human tumors, early vaccination produced a significantly delay in the onset of tumors, whereas late vaccination was completely devoid of an effect in comparison to untreated control mice.…”