Apical soft tissue biopsies predict biochemical failure in radical perineal prostatectomy patients with apical cancer involvement.

The aim of the study was to prospectively assess the role of apical soft tissue biopsies in radical perineal prostatectomy (RPP) patients with documented apical prostate cancer (PCA) involvement. Between June 1998 and May 1999, 77 consecutive men with localized PCA and documented invasion of the prostatic apex underwent RPP by a single surgeon. Soft tissue biopsies were systematically obtained from the prostatic fossa overlying the apex at the time of surgery. Time to biochemical failure was calculated using the Kaplan-Meier method. The rates of positive apical margins and positive apical soft tissue biopsies were 23.4% (18/77) and 15.6% (12/77). The sensitivity, specificity and positive predictive value of positive apical margins for residual apical disease as determined by apical soft tissue biopsy were 41.7, 80, and 28%, respectively. The overall biochemical failure rate was 28.6% (22/77) with a median follow-up of 51 months (range 3-73 months). The 36-month biochemical recurrence-free survival rate was 55.9+/-14.9% for patients with positive apical biopsies and 78.7+/-5.3% for those with negative biopsies (P=0.023). In conclusion, positive apical soft tissue biopsy is an independent predictor of biochemical failure in patients with apical PCA who undergo RPP. Positive apical surgical margins poorly predict residual apical disease that is frequently identifiable by apical soft tissue biopsy. Apical soft tissue biopsies should therefore be obtained in patients with known extensive apical cancer involvement at the time of RPP.

Human dendritic cells transfected with renal tumor RNA stimulate polyclonal T-cell responses against antigens expressed by primary and metastatic tumors.

Although renal cell carcinoma has been shown to respond to immunotherapy, renal cell carcinoma-specific rejection antigens and their corresponding CTL epitopes have rarely been described. The use of dendritic cells (DCs) transfected with mRNA isolated from tumor cells may allow specific immunotherapy even in cancers for which potent rejection antigens have not been identified. Here we show that DCs transfected with RNA isolated from renal cancer tissue are remarkably effective in stimulating tumor-specific T-cell response in vitro but do not cross-react with normal tissue antigens including antigens expressed by renal parenchyma. In contrast, the tumor-specific CTLs lysed allogeneic tumor but not allogeneic normal tissue targets, suggesting the presence of shared albeit unidentified antigens among renal carcinomas. CTL responses against telomerase reverse transcriptase (TERT) accounted in part for the reactivities against allogeneic tumors because renal tumor RNA-transfected DCs stimulated polyclonal CTL responses, which encompassed as a subcomponent a response against TERT. Nonetheless, the tumor-specific CTLs were consistently superior to the CTLs stimulated with TERT RNA-transfected DCs in recognizing and lysing tumor targets, suggesting that tumor-specific CTLs represent a polyclonal response providing more effective antitumor activity than T-cell responses directed against a single antigen in the form of TERT. Tumor RNA-transfected DCs were capable of stimulating T-cell reactivities not only against the primary tumor but also against metastatic tumors, although discrete differences in the antigenic repertoire expressed by these tissues were apparent. Thus, total tumor RNA-transfected DCs may represent a broadly applicable vaccine strategy to induce polyclonal and potentially therapeutic T-cell responses in renal cancer patients.

Comparison of ultrasound-guided biopsies and prostatectomy specimens: predictive accuracy of Gleason score and tumor site.

OBJECTIVE: To critically evaluate the accuracy of sextant biopsies in predicting Gleason score and the site of tumor location in patients with clinically localized prostate cancer treated by radical perineal prostatectomy. METHODS: The case records of 289 patients with clinically localized prostate cancer who underwent radical perineal prostatectomy were reviewed, comparing the Gleason score and tumor site location as determined by sextant ultrasound-guided core biopsies with the Gleason score and tumor distribution within the surgical specimens. The prostatectomy specimens were further characterized by extent of disease as organ-confined, specimen-confined or margin-positive. RESULTS: The Gleason score was identical in 126 (43.5%) patients. An upgrading in the surgical specimen occurred in 118 (40.8%) cases, a downgrading in 43 (14.8%). Overall, 193 (66.7%) patients had a unilateral positive biopsy, while 96 (33.2%) patients had bilateral positive biopsies. Sixty-four (33.1%) patients with a unilateral positive biopsy had cancer confined to one side of the gland, while 127 (65.8%) showed bilateral disease; 142 (73.5%) patients had organ-confined tumors versus 51 (26.4%) patients with capsular penetration. In the 96 patients with bilateral positive biopsies, 64 (66.6%) patients had intracapsular cancer versus 32 (33.3%) patients with either specimen-confined or margin-positive disease. The overall rate of positive margins was 14%. Fifty-one (61.4%) of the 83 patients with non-organ-confined disease had posterolateral capsular penetration in the region of the superior pedicle of the neurovascular bundle, while 28 (33.7%) patients had apical capsular penetration, in the region of the inferior neurovascular pedicle. CONCLUSIONS: The ability of sextant ultrasound-guided biopsies to estimate the pathological grading is satisfactory: when we consider a difference of +/- 1 in the final Gleason score, the overall correlation is 80%. In 66% of the cases, sextant biopsies predicted unilateral disease when bilateral disease existed. A unilateral positive biopsy does not predict unilateral disease.

Induction of polyclonal prostate cancer-specific CTL using dendritic cells transfected with amplified tumor RNA.

Polyvalent cancer vaccines targeting the entire antigenic spectrum on tumor cells may represent a superior therapeutic strategy for cancer patients than vaccines solely directed against single Ags. In this study, we show that autologous dendritic cells (DC) transfected with RNA amplified from microdissected tumor cells are capable of stimulating CTL against a broad set of unidentified and critical prostate-specific Ags. Although the polyclonal CTL responses generated with amplified tumor RNA-transfected DC encompassed as a subcomponent a response against prostate-specific Ag (PSA) as well as against telomerase reverse transcriptase, the tumor-specific CTL were consistently more effective than PSA or telomerase reverse transcriptase CTL to lyse tumor targets, suggesting the superiority of the polyclonal response. Although tumor RNA-transfected DC stimulated CTL, which recognized not only tumor but also self-Ags expressed by benign prostate tissue, these cross-reactive CTL were exclusively specific for the PSA, indicating an immunodominant role of PSA in the prostate cancer-specific immune response. Our data suggest that tumor RNA-transfected DC may represent a broadly applicable, potentially clinically effective vaccine strategy for prostate cancer patients, which is not limited by tumor tissue availability for Ag preparation and may minimize the risk of clonal tumor escape.

Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells.

The polypeptide component of telomerase (TERT) is an attractive candidate for a broadly expressed tumor rejection antigen because telomerase is silent in normal tissues but is reactivated in more than 85% of cancers. Here we show that immunization against TERT induces immunity against tumors of unrelated origin. Immunization of mice with TERT RNA-transfected dendritic cells (DC) stimulated cytotoxic T lymphocytes (CTL), which lysed melanoma and thymoma tumor cells and inhibited the growth of three unrelated tumors in mice of distinct genetic backgrounds. TERT RNA-transfected human DC stimulated TERT-specific CTL in vitro that lysed human tumor cells, including Epstein Barr virus (EBV)-transformed B cells as well as autologous tumor targets from patients with renal and prostate cancer. Tumor RNA-transfected DC were used as surrogate targets in the CTL assays, obviating the difficulties in obtaining tumor cells from cancer patients. In one instance, where a tumor cell line was successfully established in culture from a patient with renal cancer, the patient's tumor cells were efficiently lysed by the CTL. Immunization with tumor RNA was generally more effective than immunization with TERT RNA, suggesting that an optimal immunization protocol may have to include TERT as well as additional tumor antigens.

Outcome profiles of locoregional disease after radical prostatectomy and radiotherapy.

The purpose of the present study was to examine the outcome profiles of a large number of patients with locally advanced adenocarcinoma of the prostate following radical perineal prostatectomy (RPP) for clinically organ-confined disease. Of 1662 men who underwent RPP performed by a single surgeon between January 1972 and January 1999, 692 patients (41.6%) aged a median of 66.1 years were found to have extracapsular disease on pathological evaluation. The extent of disease was categorized as either specimen-confined (n = 355) or margin-positive (n = 337). The histological grade of the cancer was characterized using the Gleason score. Time to biochemical failure, defined as a prostate-specific antigen (PSA) level of > or = 0.5 ng/ml, and cancer-associated survival were the end points of our outcome analysis using the Kaplan-Meier product-limit method. The median time to cancer-associated death for patients with specimen-confined and margin-positive disease was 18.5 and 13.1 years, respectively. After 5 years, 37% and 54% of the patients with specimen-confined and margin-positive disease, respectively, had PSA failure. Prostate cancer patients with a Gleason score of 5-6, 7, and 8-10 experienced a median time to cancer-associated death of 19.9, 19.2, and 10.5 years, respectively. A subset of patients undergoing adjunctive radiation therapy (XRT) relapsed biochemically after a median period of approximately 18 months. RPP provides a substantial disease-control benefit in patients with specimen-confined cancer. The time to biochemical failure and the time to cancer-associated death are significantly influenced by the biology of the underlying disease, necessitating long-term follow-up in the outcome analysis of any modality of treatment for prostate cancer. A benefit of early adjunctive XRT for local failure remains to be determined.

The evolving role of dendritic cell therapy in urologic oncology.

The recognition that dendritic cells, the most potent antigen-presenting cells, play a pivotal role in the induction of antitumor immunity has reshaped the development of tumor vaccines in clinical medicine. Early clinical trials of administration of dendritic cell-based vaccines to patients with genitourinary malignancies showed low toxicity profiles, and provided evidence for immunologic and clinical responses in some patients. Although the development of dendritic cell-based vaccines is still in its infancy, the prospects of ultimately generating clinically effective cancer vaccines have become more realistic.

Radical cystectomy for invasive bladder cancer: contemporary results and remaining controversies.

The impact of stage progression of superficial cancer to invasive disease is profound. However, the optimal-timed management of invasive bladder cancer is still controversial. Pelvic lymph node dissection and radical cystectomy are considered to be the optimal therapy regarding local tumor control and ultimate cure of cancer, whereas chemotherapy offers the only viable but limited option for patients with distant metastasis or locally advanced disease. Identification of conventional and molecular prognostic factors to predict cancer-specific survival following radical cystectomy is one important step to identify candidates that may benefit from early cystectomy or adjunct chemotherapy. With this background, the results of historic and contemporary radical cystectomy series for carcinoma of the bladder are reviewed.

Outcome analysis in patients with primary necrotizing fasciitis of the male genitalia.

OBJECTIVES: To characterize patients with primary necrotizing fasciitis of the male genitalia (Fournier's gangrene) and to identify risk factors and prognostic variables of survival. METHODS: Fifty consecutive patients with primary necrotizing fasciitis of the male genitalia treated at our institution during a 15-year period between 1984 and 1998 were retrospectively analyzed. Of these patients, 44 (88.0%) were found to be eligible for analysis of the outcome parameters. Univariate survival analysis was performed using the Kaplan-Meier algorithm followed by multivariate analysis of statistically significant variables. Six patients (12.0%) who were severely immunocompromised were studied separately. RESULTS: Medical comorbidities were prevalent, with diabetes being the most common condition (50%). The overall mortality rate was 20% (10 of 50). Three statistically significant predictors of outcome were identified among the variables analyzed. These were the extent of the infection (P = 0.0262), the depth of the necrotizing infection (P = 0.0107), and treatment with hyperbaric oxygen (P = 0.0115). Multivariate regression analysis of these variables identified the extent of the infection (P = 0.0234) as the only statistically significant, independent predictor of outcome in the presence of other covariables. CONCLUSIONS: The involved body surface area appears to be the most important prognostic variable, with a significant impact on outcome. Given the high mortality of the disease entity and a trend toward the improved survival of patients receiving hyperbaric oxygen, this treatment form appears indicated in more severe cases. Immunocompromised patients, who frequently have an atypical and fulminant clinical course, appear to constitute a separate group with a dismal prognosis.

Human dendritic cells transfected with RNA encoding prostate-specific antigen stimulate prostate-specific CTL responses in vitro.

Although immunological tolerance to self Ags represents an important mechanism to prevent normal tissue injury, there is growing evidence that tolerance to tumor Ags, which often represent normal peripherally expressed proteins, is not absolute and can be effectively reverted. Prostate-specific Ag (PSA) is a self Ag expressed by both normal and malignant prostatic epithelium, and therefore offers a unique opportunity to examine the ability of self Ags to serve as specific CTL targets. In this study, we investigated the efficacy of autologous dendritic cells (DC) transfected with mRNA encoding PSA to stimulate CTL against PSA Ags in vitro. Ag in form of RNA carries the advantage to encode multiple epitopes for many HLA alleles, thus permitting induction of CTL responses among many cancer patients independent of their HLA repertoire. In this study, we show that PSA mRNA-transfected DC were capable of stimulating primary CTL responses against PSA Ags in vitro. The PSA-specific CTL did not cross-react with kallikrein Ags, a protein, which shares significant homology with PSA, suggesting that harmful autoimmune toxicity may not represent a significant problem with this approach. PSA RNA-transfected DC generated from male or female healthy volunteers or from cancer patients were equally effective in stimulating PSA-specific CTL in vitro, implying that neither natural tolerance to PSA Ags nor tumor-mediated T cell anergy may represent major barriers for CTL generation against the self Ag PSA. This study provides a preclinical rationale for using PSA RNA-transfected DC in active or adoptive immunization protocols.

The impact of primary stage on survival in patients with lymph node positive bladder cancer.

PURPOSE: Contemporary series indicate that survival of cystectomy candidates with node positive bladder cancer is favorable when the primary tumor is confined to the bladder wall and lymph node involvement is minimal. However, these series lack node negative controls with a similar tumor stage to determine accurately the true impact of pelvic lymphadenectomy and radical cystectomy on survival. MATERIALS AND METHODS: We retrospectively analyzed disease specific survival in 686 consecutive cystectomy candidates of whom 193 (28.1%) had node positive disease at radical cystectomy. To correct for bias towards higher P category in the node positive group we subdivided groups into organ and nonorgan confined categories to compare outcome between node negative and node positive cases. RESULTS: The frequency of organ confined disease in node positive cases was 22.8% compared to 59.2% in node negative cases. Although when analyzing the entire group disease specific survival was significantly decreased in node positive cases, after correction for P stage we found no statistically significant differences in survival between N0 and N1 cases in the organ confined group (p = 0.4267). Differences between N0 and N1 cases in nonorgan confined disease were statistically significant (p = 0.0276). Significance levels were more pronounced when cases with N2 or N3 categories were compared with node negative cases. Comparison of survival between node negative and N2 or N3 in either group revealed significant differences indicating limited impact of surgery alone at this disease stage. CONCLUSIONS: Patients with N1 disease seem to benefit from pelvic lymphadenectomy and radical cystectomy as evidenced by similar outcome in those with node negative disease and similar P stage of the primary tumor. However, the observed benefit rapidly disappears when more than 1 lymph node is involved and additional therapy other than surgery seems appropriate.

Pelvic lymph node dissection can be curative in patients with node positive bladder cancer.

PURPOSE: We analyze outcome in a large cohort of patients with bladder cancer metastatic to the regional lymph nodes using disease specific survival as the end point. MATERIALS AND METHODS: To identify predictors for outcome a large series of 193 consecutive patients with regional lymph node metastases operated on from 1980 to 1990 at Memorial Sloan-Kettering Cancer Center was retrospectively analyzed. RESULTS: Among various clinical and pathological parameters, univariate and multivariate analyses identified only P (p = 0.0001) and N categories (p = 0.0006) as parameters predicting disease specific survival. In patients who received chemotherapy or irradiation either as part of a nonrandomized clinical protocol or on an ad hoc basis no beneficial impact on disease specific survival could be demonstrated. Survival was also not affected by pathological grade and other histological parameters, since pathological features in patients with node positive bladder cancer are uniformly shifted towards high grade lesions with vascular or lymphatic invasion and a solid appearance on histological analysis. CONCLUSIONS: Nodal metastases carry a poor prognosis despite pelvic lymphadenectomy and radical cystectomy. Nevertheless, some node positive cases with otherwise localized bladder cancer and/or low N category appear to benefit from surgery. Our findings of improved outcome in some individuals with node positive disease should be considered in the design of clinical trials evaluating the effects of adjuvant or neoadjuvant treatment strategies, and emphasize the importance of randomized studies to assess the results of these approaches.

Interobserver variability in the interpretation of unenhanced helical CT for the diagnosis of ureteral stone disease.

PURPOSE: The purpose of this study was to analyze interobserver agreement in the interpretation of unenhanced helical CT (UHCT) for the evaluation of ureteral stone disease and obstruction. METHOD: One hundred three UHCT examinations were independently and retrospectively reviewed by five readers including attending radiologists, a radiology resident, and an attending urologist. Examinations were interpreted as positive, negative, or indeterminate for ureteral stone disease and obstruction. The Cohen kappa test was used to measure interobserver agreement. The accuracy of the readers was also assessed. RESULTS: The kappa value ranged from 0.67 to 0.71 among the three attending radiologists and from 0.65 to 0.67 among the radiology attending physicians and radiology resident. Although the urologist tended to agree less well with the other readers (kappa range: 0.33-0.46), there was no statistically significant difference (p < 0.05) in the accuracy among all five readers. The percentage of cases interpreted as indeterminate ranged from 8 to 25% and almost invariably involved difficulty distinguishing phleboliths from minimally obstructing distal ureteral calculi. The percentage of UHCT scans correctly interpreted as positive and correctly interpreted as negative ranged from 73% (n = 27) to 86% (n = 32) and 63% (n = 22) to 86% (n = 30), respectively. CONCLUSION: Interobserver agreement was very good among the radiology attending physicians and resident and moderate with the urologist. The examination is an accurate technique in the evaluation of ureteral stone disease, although limitations exist, particularly in the diagnosis of minimally obstructing distal ureteral calculi.

Transient lower extremity neurapraxia associated with radical perineal prostatectomy: a complication of the exaggerated lithotomy position.

PURPOSE: We assess the incidence and risk factors associated with lower extremity neurapraxia following radical perineal prostatectomy. MATERIALS AND METHODS: The medical records of 111 consecutive patients undergoing radical perineal prostatectomy at Duke University Medical Center between June 1994 and June 1995 were retrospectively reviewed. Patients were interviewed by telephone to ascertain whether symptoms had resolved. RESULTS: Neurapraxia developed in 23 patients (21%). Symptomatology was variable, including sensory and motor deficits of the lower leg and foot. Although lower extremity neurapraxia occurred in a significant number of patients undergoing radical perineal prostatectomy, it appeared to resolve in most. CONCLUSIONS: Careful attention to detail when positioning the patient and limiting the time in the exaggerated lithotomy position appear to be the most critical aspects to prevent neurapraxia.

Unenhanced helical computerized tomography for the evaluation of patients with acute flank pain.

PURPOSE: We determined the value of unenhanced helical computerized tomography (CT) in the diagnosis of acute flank pain in 105 patients evaluated for suspected stone disease. MATERIALS AND METHODS: Noncontrasted spiral CT was done in 105 consecutive patients seen in our emergency department to evaluate acute flank pain. All CT studies were reviewed for the presence of ureteral or renal calculi, perinephric or periureteral stranding, presence and degree of pelvicalicectasis or other radiological findings. If necessary, an excretory urogram was performed to confirm the presence or absence of urinary stones. Patients were followed to determine clinical outcome including the need for urological intervention. RESULTS: Of the 49 patients determined to have stones 24 (49%) had spontaneous stone passage, 10 (20%) had improved symptoms without documented stone passage and 14 (29%) required surgical intervention. In 29 of 51 patients (57%) with negative CT readings for stone disease a diagnosis was established by other intra-abdominal findings. In 21 patients (41%) no clinical diagnosis could be established, and 1 scan in a patient with a distal ureteral calculus was interpreted as falsely positive. These findings yielded a sensitivity of 98%, specificity 98% and overall accuracy 96% for diagnosing ureteral stones. CONCLUSIONS: Despite the limitations of helical CT in evaluating renal function and nonobstructing ureteral calculi, noncontrasted CT is a sensitive imaging modality for the detection of urinary tract calculi and obstruction. The majority of our patients required no further imaging to determine the need for urological intervention. At our institution spiral CT has become the standard method to evaluate patients with acute flank pain leading to more rapid turnover in the emergency department at similar or even reduced cost to conventional excretory urography.

Does prostate transitional cell carcinoma preclude orthotopic bladder reconstruction after radical cystoprostatectomy for bladder cancer?

PURPOSE: We determined if urethral preservation and orthotopic bladder replacement in patients with transitional cell carcinoma within the prostatic urethra or prostate placed these patients at risk for urethral recurrence or death. MATERIALS AND METHODS: The clinical course of all patients undergoing urethral preservation and orthotopic bladder replacement was reviewed. The urethra was sacrificed only if the distal prostatic urethral margin was positive for transitional cell carcinoma. The pathological T stage and the grade of the primary malignancy, local recurrence, site of recurrence (urethral, pelvic, distant) and death were documented. RESULTS: Of 81 patients 70 were evaluable (June 1996) with a mean followup of 35 months. Of the 70 patients 48 were alive without evidence of disease for a mean of 38 months (range 8 to 107) and 5 died without evidence of disease. Eight of these 53 patients (15%) had prostatic involvement (carcinoma in situ in 6, intraductal carcinoma in 1 and stromal invasive transitional cell carcinoma in 1). Of the 70 patients 17 had disease recurrence (13 died of disease and 4 are alive, 1 of whom had urethral recurrence without initial prostatic transitional cell carcinoma). Of the 17 patients (35%) 6 had transitional cell carcinoma prostatic involvement (carcinoma in situ in 4 and stromal invasion in 2), and 5 of these 6 died, none with or of urethral recurrence but of the primary bladder pathology. Of these 5 patients 1 had stromal invasive transitional cell carcinoma of the prostate and experienced a bulbar urethra recurrence at 1 month and a pelvic recurrence at 3 months, and died at 5 months. Death was not secondary to the urethral recurrence. Thus, of the 14 patients who had prostatic transitional cell carcinoma, only 1 had urethral recurrence (7%), and this recurrence did not present as the cause of death. CONCLUSIONS: The guidelines for urethral resection can be relaxed, increasing the opportunities for orthotopic reconstruction, without placing the patients at increased risk for death of transitional cell carcinoma.

[Basic principles of gene therapy]. / Grundlagen der Gentherapie.

The rapid development of recombinant DNA technology and our enhanced understanding of the genetic basis of human disease has facilitated the development of new molecular therapeutic modalities, termed gene therapy. Gene therapy involves the transfer of functional genes into somatic cells and their expression in target tissues in order to replace absent genes, correct defective genes, or induce antitumoral activity in the tumor-bearing host. Currently, an increasing number of gene therapy strategies are being investigated in experimental and clinical trials. Despite substantial progress, a number of technical and logistical hurdles must still be overcome before gene therapy can be safety and effectively applied in the human patient. Since gene therapy involves complex cell processing and can be time consuming and costly, simplifications or even alternative approaches will be necessary in order to establish this therapy as suitable for clinical use. This report reviews various gene therapy strategies and gene delivery techniques currently under clinical or experimental investigation. Special emphasis is given to cytokine gene therapy using gene-modified tumor vaccines for cancer treatment.

Efficient gene transfer with adeno-associated virus-based plasmids complexed to cationic liposomes for gene therapy of human prostate cancer.

We have shown previously that treatment of rats bearing the Dunning R3327 MatLyLu prostatic tumor with human interleukin 2 (IL-2) gene-modified tumor cell preparations induces potent antitumor immunity in the animal. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of prostate cancer, we have explored the use of a simplified gene delivery system based on liposomes to introduce and express the IL-2 gene in the Dunning rat R3327 MatLyLu prostatic tumor cell line (MatLyLu) and in short-term cultures of primary human prostatic tumor cells. Liposome-DNA complexes containing the adeno-associated virus inverted terminal repeats exhibited 3-10-fold higher levels of gene transfer and IL-2 expression than did liposome complexes with non-adeno-associated virus containing plasmids. Single transfections resulted in IL-2 expression for an extended period of time that exceeded severalfold the amount of IL-2 secreted from retrovirally transduced MatLyLu cells. X-irradiation of cells (4000 rads) prior to transfection did not affect cytokine secretion, indicating that liposome-mediated gene transfer does not depend on cell proliferation. High levels of gene transfer and IL-2 expression were also achieved in short-term cultures of primary human prostatic tumor cells established from tumor specimens obtained following radical prostatectomy of cancer patients. Depending on the type of liposome used, IL-2 levels secreted from the human prostatic tumor cells were comparable to or exceeded the levels of IL-2 secreted from retrovirally transduced MatLyLu cells, which induced antitumor immunity in the rat model. The ability to culture and expand ex vivo human prostatic tumor cells, and the use of a simple and highly efficient gene transfer method to generate genetically modified tumor vaccines, set the stage for clinical exploration of gene-based immunotherapy of prostate cancer.