***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: This study was conducted in prostate cancer patients in biochemical relapse after radical prostatectomy , to assess the feasibility , safety , and immunogenicity of therapeutic vaccination with autologous dendritic cells ( DCs ) pulsed with human recombinant prostate-specific antigen ( PSA ) ( Dendritophage-rPSA ) .  Twenty-four patients with histologically proven prostate carcinoma and an isolated postoperative rise of serum PSA ( > 1 ng/ml to 10 ng/ml ) after radical prostatectomy were included . The patients received nine administrations of PSA-loaded DCs by combined intravenous , subcutaneous , and intradermal routes over 21 weeks . Postbaseline blood tests were performed at months 1 , 3 , 6 , 9 , and 12 ( PSA levels ) , at months 6 and 12 ( circulating prostate cancer cells ) , at month 6 ( anti-PSA IgG and IgM antibodies ) , and at up to eight time points before , during , and after immunization ( PSA-specific T cells ) . Circulating prostate cancer cells detected in six patients at baseline were undetectable at 6 months and remained undetectable at 12 months . Eleven patients had a postbaseline transient PSA decrease on one to three occasions , predominantly occurring at month 1 ( 7 patients ) or month 3 ( 2 patients ) . Maximum PSA decrease ranged from 6 % to 39 % . PSA decrease on at least one occasion was more frequent in patients with low Gleason score ( p=0.016 ) at prostatectomy and with positive skin tests at study baseline ( p=0.04 ) . PSA-specific T cells were detected ex vivo by ELISpot for IFN-γ in 7 patients before vaccination and in 11 patients after vaccination . Of the latter 11 patients , 5 had detectable T cells both before and during the vaccination period , 4 only during the vaccination period , while 2 patients could for technical reasons not be assessed prevaccination . No induction of anti-PSA IgG or IgM antibodies was detected . There were no serious adverse events or otherwise severe toxicities observed during the trial . Immunization with Dendritophage-rPSA  was feasible and safe in this cohort of patients . An immune response specific for PSA could be detected in some patients . A notable effect was the disappearance of circulating prostate cells in all patients who were RT-PCR positive before vaccination Sipuleucel‐T is an investigational active cellular immunotherapy product design ed to stimulate an immune response against prostate cancer . The safety and efficacy  of sipuleucel‐T was evaluated in 2 identically design ed , r and omized , double‐blind , placebo‐controlled trials ( D9901 and D9902A ) conducted in men with advanced prostate cancer We attempted to induce therapeutic immunity against prostate-derived tissues in patients suffering from progressive hormone-refractory metastatic prostate carcinoma . Thirteen patients were treated with two infusions , 1 month apart , of autologous dendritic cells ( APC8015 ) preexposed ex vivo to PA2024 , a fusion protein consisting of human granulocyte/macrophage-colony stimulating factor ( GM-CSF ) and human prostatic acid phosphatase ( PAP ) . The infusions were followed by three s.c . monthly doses of PA2024 without cells .  Three groups of patients each received PA2024 at 0.3 , 0.6 , or 1.0 mg/injection . All Ps were two-sided . Treatment was well tolerated . After infusions of APC8015 , patients experienced only mild ( grade 1 - 2 ) short-lived fever and /or chills , myalgia , pain , and fatigue . One patient developed grade 3 fatigue . Four patients developed mild local reactions to s.c . PA2024 . Twelve patients were evaluable for response to treatment . Circulating prostate-specific antigen levels dropped in three patients . T cells , drawn from patients after infusions of APC8015 , but not before , could be stimulated in vitro by GM-CSF ( P = 0.0004 ) and PAP ( P = 0.0001 ) , demonstrating broken immune tolerance against these two normal proteins . Injections of PA2024 did not influence the reactivity of T cells against PAP and GM-CSF . However , antibodies to GM-CSF and , to a much lesser extent , to PAP reached maximum titers only after two or even three injections of PA2024 , showing that directly injected PA2024 was involved in stimulation of humoral immunity . Dendritic cells exposed to antigen ex vivo can induce antigen-specific cellular immunity in prostate cancer patients , warranting further studies of this mode of immunotherapy CFSE dye dilution analysis and [ 3H ] thymidine incorporation were used side by side to assess proliferative responses of peripheral blood mononuclear cells ( P BMC s ) after vaccination of renal cell carcinoma patients ( n=6 ) with antigen-loaded dendritic cells . Immune responses against the control antigen keyhole limpet hemocyanin ( KLH ) were induced in all patients . While [ 3H ] thymidine incorporation revealed a 4 to 977-fold increase in KLH-induced proliferation ( mean : 209-fold ) , CFSE-labeling experiments demonstrated that the KLH-responsive population of postvaccination P BMC s represented 7–53 % ( mean : 23 % ) . Combining CFSE-labeling with T-cell subset analysis confirmed the presence of CD4 + KLH-reactive T cells but also revealed a substantial population of CD8 + KLH-reactive T cells in one patient as well as minor population s of CD8 + KLH-reactive T cells in three other patients . Our data indicate that CFSE dye dilution analysis is a valuable tool for immune monitoring after dendritic cell vaccination Immunostimulatory properties of dendritic cells ( DCs ) are linked to their maturation state . Injection of mature DCs rapidly enhances antigen-specific CD4 + and CD8 + T cell immunity in humans . Here we describe the immune response to a single injection of immature DCs pulsed with influenza matrix peptide ( MP ) and keyhole limpet hemocyanin ( KLH ) in two healthy subjects . In contrast to prior findings using mature DCs , injection of immature DCs in both subjects led to the specific inhibition of MP-specific CD8 + T cell effector function in freshly isolated T cells and the appearance of MP-specific interleukin 10–producing cells . When pre- and postimmunization T cells were boosted in culture , there were greater numbers of MP-specific major histocompatibility complex tetramer-binding cells after immunization , but these had reduced interferon γ production and lacked killer activity . These data demonstrate the feasibility of antigen-specific inhibition of effector T cell function in vivo in humans and urge caution with the use of immature DCs when trying to enhance tumor or microbial immunity Background : Dendritic cell (DC)-based immunotherapy is a promising approach to augment tumor antigen-specific T cell responses in cancer patients . However , tumor escape with down-regulation or complete loss of target antigens may limit the susceptibility of tumor cells to the immune attack . Concomitant generation of T cell responses against several immunodominant antigens may circumvent this potential drawback . In this trial , we determined the immunostimulatory capacity of autologous DC pulsed with multiple T cell epitopes derived from four different prostate-specific antigens in patients with advanced hormone-refractory prostate cancer . Patients and methods : Autologous DC of HLA-A*0201 + patients with hormone-refractory prostate cancer were loaded with antigenic peptides derived from prostate stem cell antigen ( PSCA14–22 ) , prostatic acid phosphatase ( PAP299–307 ) , prostate-specific membrane antigen ( PSMA4–12 ) , and prostate-specific antigen ( PSA154–163 ) . DC were intradermally applied six times at biweekly intervals followed — in the case of an enhanced immune response — by monthly booster injections . Immune monitoring during the time of ongoing vaccinations ( 12–59 weeks ) included ex vivo ELISPOT measurements , MHC tetramer analysis and in vitro cytotoxicity assays . Results : Of the initial six patients , three qualified for long-term multi-epitope DC vaccination . This regime was tolerated well by all three patients . The vaccination elicited significant cytotoxic T cell responses against all prostate-specific antigens tested . In addition , memory T cell responses against the control peptides derived from influenza matrix protein and tetanus toxoid were efficiently boosted . Clinical ly , the long-term DC vaccination was associated with an increase in PSA doubling time . Conclusions : DC-based multi-epitope immunotherapy with repeated boosting in men with hormone-refractory prostate carcinoma is feasible and generates efficient cellular antitumor responses Many tumor-associated Ags represent tissue differentiation Ags that are poorly immunogenic . Their weak immunogenicity may be due to immune tolerance to self-Ags . Prostatic acid phosphatase ( PAP ) is just such an Ag that is expressed by both normal and malignant prostate tissue . We have previously demonstrated that PAP can be immunogenic in a rodent model . However , generation of prostate-specific autoimmunity was seen only when a xenogeneic homolog of PAP was used as the immunogen . To explore the potential role of xenoantigen immunization in cancer patients , we performed a phase I clinical trial using dendritic cells pulsed with recombinant mouse PAP as a tumor vaccine . Twenty-one patients with metastatic prostate cancer received two monthly vaccinations of xenoantigen-loaded dendritic cells with minimal treatment-associated side effects . All patients developed T cell immunity to mouse PAP following immunization . Eleven of the 21 patients also developed T cell proliferative responses to the homologous self-Ag . These responses were associated with Ag-specific IFN-γ and /or TNF-α secretion , but not IL-4 , consistent with induction of Th1 immunity . Finally , 6 of 21 patients had clinical stabilization of their previously progressing prostate cancer . All six of these patients developed T cell immunity to human PAP following vaccination . These results demonstrate that xenoantigen immunization can break tolerance to a self-Ag in humans , result ing in a clinical ly significant antitumor effect BACKGROUND Organ-confined renal-cell carcinoma is associated with tumour progression in up to 50 % of patients after radical nephrectomy . At present , no effective adjuvant treatment is established . We aim ed to investigate the effect of an autologous renal tumour cell vaccine on risk of tumour progression in patients with stage pT2 - 3b pN0 - 3 M0 renal-cell carcinoma . METHODS Between January , 1997 , and September , 1998 , 558 patients with a renal tumour scheduled for radical nephrectomy were enrolled at 55 institutions in Germany . Before surgery , all patients were central ly r and omised to receive autologous renal tumour cell vaccine ( six intradermal applications at 4-week intervals postoperatively ; vaccine group ) or no adjuvant treatment ( control group ) . The primary endpoint of the trial was to reduce the risk of tumour progression , defined as progression or death . All patients were assessed after st and ardised diagnostic investigations at 6-month intervals for a minimum of 4.5 years . FINDINGS By preoperative and postoperative inclusion criteria , 379 patients were assessable for the intention-to-treat analysis . At 5-year and 70-month follow-up , the hazard ratios for tumour progression were 1.58 ( 95 % CI 1.05 - 2.37 ) and 1.59 ( 1.07 - 2.36 ) , respectively , in favour of the vaccine group ( p=0.0204 , log-rank test ) . 5-year and 70-month progression-free survival rates were 77.4 % and 72 % , respectively , in the vaccine group and 67.8 % and 59.3 % , respectively , in the control group . The vaccine was well tolerated , with only 12 adverse events associated with the treatment . INTERPRETATION Adjuvant treatment with autologous renal tumour cell vaccine in patients with renal-cell carcinoma after radical nephrectomy seems to be beneficial and can be considered in patients undergoing radical nephrectomy due to organ-confined renal-cell carcinoma of more than 2.5 cm in diameter PURPOSE Prostate-specific antigen ( PSA ) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells . For patients with metastatic disease , changes in PSA will often ante date changes in bone scan . Furthermore , many but not all investigators have observed an association between a decline in PSA levels of 50 % or greater and survival . Since the majority of phase II clinical trials for patients with and rogen-independent prostate cancer ( AIPC ) have used PSA as a marker , we believed it was important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting . We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters . RESULT We defined four patient groups : ( 1 ) progressive measurable disease , ( 2 ) progressive bone metastasis , ( 3 ) stable metastases and a rising PSA , and ( 4 ) rising PSA and no other evidence of metastatic disease .  
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/ SIGNIFICANCE As a ' proof of principle ' a statistically significant effect of DC-mediated cellular immune response and of DC dose on CBR could be demonstrated .