***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: The effect of cancer immunotherapies is on the immune system and not directly on the tumour . The kinetics of immunotherapy are characterised by a cellular immune response followed by potential changes in tumour burden or patient survival . To adequately investigate immunotherapies in clinical trials , a new development paradigm including reconsideration of established end points addressing this biology is needed . Over the last 7 years , several initiatives across the cancer immunotherapy community were facilitated by the Cancer Research Institute Cancer Immunotherapy Consortium . They systematic ally evolved an immunotherapy-focused clinical development paradigm and proposed to redefine trial end points . On that basis , analysis of several large data sets generated throughout the immunotherapy community supports three novel end point proposals . First , results from T-cell immune response assays are highly variable and often nonreproducible . Harmonisation of assays can minimise this variability and support the investigation of the cellular immune response as a biomarker and testing it for clinical surrogacy . Secondly , immunotherapy induces novel patterns of the antitumour response not captured by World Health Organisation criteria or Response Evaluation Criteria in Solid Tumours . New immune-related response criteria were defined which more comprehensively capture all response patterns . Thirdly , survival curves in r and omised immunotherapy trials can show a delayed separation , which can impact study results . Altered statistical models are needed to describe the hazard ratios as a function of time , and differentiate them before and after separation of curves to improve planning of phase III trials . Taken together , these recommendations may improve our tools for cancer immunotherapy investigations We have completed a multicenter , r and omized controlled phase III clinical trial in Stages II and III colon cancer patients with active specific immunotherapy ( ASI ) using autologous tumor cells with an immunomodulating adjuvant bacillus Callmette-Guerin ( BCG ) vaccine ( OncoVAX ) in an adjuvant setting . In this study , patients were r and omized to receive either OncoVAX therapy or no therapy after surgical resection of the primary tumor and stratified by stage of disease . Since the biologic essence of the effective tumor immunotherapy is the presence in the vaccine of a minimum number of viable , metabolically active , autologous tumor cells , the processing of the vaccine product , occurred within 48 h after surgery . Analysis of prognostic benefit in the pivotal phase III trial , with a 5.8 year median follow-up , showed that a beneficial effect of OncoVAX is statistically significant for all endpoints including recurrence-free interval , overall survival , and recurrence-free survival in Stage II colon cancer patients . Surgery alone cures approximately 65 % of Stage II ( Dukes B2 , B3 ) colon cancer patients . In the remaining patients , OncoVAX in an adjuvant setting , significantly prolongs recurrence-free interval ( 57.1 % relative risk reduction ) and significantly improves 5-year overall survival and recurrence-free survival . No statistically significant prognostic benefits were achieved in Stage III ( Duke 's C1-C3 ) patients . A health economics assessment was performed on these results in Stage II colon cancer patients using disease-free survival and overall survival ( for the entire intent-to-treat population ) . Cost-effectiveness , cost-utility and sensitivity analysis were applied with , cost of life years , recurrence-free life years and quality adjusted life years ( QALYs ) as the primary endpoints to this analysis . The perspective of the economic analysis was the current direct medical cost established by the health care providers . The introduction of new technologies often leads to additional costs . This report verified that the use of OncoVAX for patients with Stage II colon cancer not only has significant prognostic benefit and positive clinical outcomes , but also showed that OncoVAX therapy yields impressive health economics benefits PURPOSE Prognosis of patients with glioblastoma is poor . Therefore , in glioblastoma patients , we analyzed whether antitumor vaccination with a virus-modified autologous tumor cell vaccine is feasible and safe . Also , we determined the influence on progression-free survival and overall survival and on vaccination-induced antitumor reactivity . PATIENTS AND METHODS In a nonr and omized study , 23 patients were vaccinated and compared with nonvaccinated controls ( n = 87 ) .  Vaccine was prepared from patient 's tumor cell cultures by infection of the cells with Newcastle Disease Virus , followed by gamma-irradiation , and applied up to eight times .  Antitumor immune reactivity was determined in skin , blood , and relapsed tumor by delayed-type hypersensitivity skin reaction , ELISPOT assay , and immunohistochemistry , respectively . RESULTS Establishment of tumor cell cultures was successful in approximately 90 % of patients . After vaccination , we observed no severe side effects . The median progression-free survival of vaccinated patients was 40 weeks ( v 26 weeks in controls ; log-rank test , P = .024 ) , and the median overall survival of vaccinated patients was 100 weeks ( v 49 weeks in controls ; log-rank test , P < .001 ) . Forty-five percent of the controls survived 1 year , 11 % survived 2 years , and there were no long-term survivors ( > or = 3 years ) . Ninety-one percent of vaccinated patients survived 1 year , 39 % survived 2 years , and 4 % were long-term survivors . In the vaccinated group , immune monitoring revealed significant increases of delayed-type hypersensitivity reactivity , numbers of tumor-reactive memory T cells , and numbers of CD8(+ ) tumor-infiltrating T-lymphocytes in secondary tumors . CONCLUSION Postoperative vaccination with virus-modified autologous tumor cells seems to be feasible and safe and to improve the prognosis of patients with glioblastomas . This could be substantiated by the observed antitumor immune response Purpose : Immunotherapeutic agents produce antitumor effects by inducing cancer-specific immune responses or by modifying native immune processes . Result ing clinical response patterns extend beyond those of cytotoxic agents and can manifest after an initial increase in tumor burden or the appearance of new lesions ( progressive disease ) . Response Evaluation Criteria in Solid Tumors or WHO criteria , design ed to detect early effects of cytotoxic agents , may not provide a complete assessment of immunotherapeutic agents . Novel criteria for the evaluation of antitumor responses with immunotherapeutic agents are required . Experimental Design : The phase II clinical trial program with ipilimumab , an antibody that blocks CTL antigen-4 , represents the most comprehensive data set available to date for an immunotherapeutic agent . Novel immune therapy response criteria proposed , based on the shared experience from community workshops and several investigators , were evaluated using data from ipilimumab phase II clinical trials in patients with advanced melanoma . Results : Ipilimumab monotherapy result ed in four distinct response patterns : ( a ) shrinkage in baseline lesions , without new lesions ; ( b ) durable stable disease ( in some patients followed by a slow , steady decline in total tumor burden ) ; ( c ) response after an increase in total tumor burden ; and ( d ) response in the presence of new lesions . All patterns were associated with favorable survival . Conclusion : Systematic criteria , design ated immune-related response criteria , were defined in an attempt to capture additional response patterns observed with immune therapy in advanced melanoma beyond those described by Response Evaluation Criteria in Solid Tumors or WHO criteria . Further prospect i ve evaluations of the immune-related response criteria , particularly their association with overall survival , are warranted . ( Clin Cancer Res 2009;15(23):7412–20 BACKGROUND Colon cancer is curable by surgery , but cure rate depends on the extent of disease . We investigated whether adjuvant active specific immunotherapy ( ASI ) with an autologous tumour cell-BCG vaccine with surgical resection was more beneficial than resection alone in stage II and III colon cancer . METHODS In a prospect i ve r and omised trial , 254 patients with colon cancer were r and omly assigned postoperative ASI or no adjuvant treatment .  ASI was three weekly vaccinations starting 4 weeks after surgery , with a booster vaccination at 6 months with 10(7 ) irradiated autologous tumour cells . The first vaccinations contained 10(7 ) BCG organisms . We followed up patients for time to recurrence , and recurrence-free and overall survival . Analysis was by intention to treat . FINDINGS The 5.3 year median follow-up ( range 8 months to 8 years 11 months ) showed 44 % ( 95 % CI 7 - 66 ) risk reduction for recurrence in the recurrence-free period in all patients receiving ASI ( p=0.023 ) . Overall , there were 40 recurrences in the control group and 25 in the ASI group . Analysis by stage showed no significant benefit of ASI in stage III disease . The major impact of ASI was seen in patients with stage II disease , with a significantly longer recurrence-free period ( p=0.011 ) and 61 % ( 18 - 81 ) risk reduction for recurrences . Recurrence-free survival was significantly longer with ASI ( 42 % risk reduction for recurrence or death [ 0 - 68 ] , p=0.032 ) and there was a trend towards improved overall survival . INTERPRETATION ASI gave significant clinical benefit in surgically resected patients with stage II colon cancer . ASI has minimal adverse reactions and should be considered in the management of stage II colon cancer Active specific immunotherapy , using vaccines with autologous tumour cells and BCG , significantly reduces the rate of tumour recurrence in stage II colon cancer patients , while no clinical benefit has yet been observed in stage III patients .  Adjuvant treatment with 5-Fluorouracil/Leucovorin is now considered st and ard therapy for stage III colon carcinoma and results in an absolute survival benefit of approximately 10 % . Yet , the 5-year overall survival rate of stage III colon cancer patients is only 40–50 % . Combining chemotherapy and immunotherapy might improve prognosis for stage III patients , especially when considering that active specific immunotherapy and chemotherapy have shown synergistic effects in pre- clinical tumour models . We performed a phase II study with 56 patients , using the combination of active specific immunotherapy and chemotherapy as an adjuvant therapy in stage III colon cancer patients to assess the influence of 5-Fluorouracil/Leucovorin on anti-tumour immunity induced by autologous tumour cell vaccinations . Anti-tumour immunity was measured before and after chemotherapy by means of delayed type hypersensitivity reactions , taken 48 h after the third and the fourth vaccination . We also investigated the toxicity of this combined immuno-chemotherapy treatment . Delayed type hypersensitivity reactions before chemotherapy had a median size of 20.3 mm , while after chemotherapy delayed type hypersensitivity size was 18.4 mm ( P=0.01 ) , indicating that chemotherapy hardly affected anti-tumour immunity . The severity of ulcers at the BCG vaccination sites was comparable to previous studies . In 30 % of the patients grade III or grade IV chemotherapy related toxicity was seen ; this is comparable to what is normally observed after adjuvant chemotherapy alone . This study shows that the active specific immunotherapy-induced anti-tumour immune response is only minimally impaired by consecutive chemotherapy and that the combined treatment of stage III colon cancer patients with active specific immunotherapy and 5-Fluorouracil/Leucovorin does not cause unexpected toxicity An active specific immunization ( ASI ) procedure with two types of autologous tumor cell vaccines ( ATVs ) is tested for adjuvant immunotherapy of resected colorectal carcinoma to provide preliminary information on local immunological skin responses , side effects , and 2-year survival rates . For vaccine preparation , the tumor-derived freshly isolated and cryopreserved cells were thawed , purified by Percoll density centrifugation , and depleted of tumor-infiltrating lymphocytes by immunomagnetic beads . After inactivation by 200 Gy , the cells of this ATV were either infected by Newcastle disease virus ( NDV ) or they were admixed with Bacillus Calmette Guérin ( BCG ) organisms . Vaccination was performed in the arm beginning 6 - 8 weeks after operation , three times at 2-week intervals . Of 57 patients that received ASI , 48 were treated by virus-infected ATV ( ATV-NDV ) and 9 were treated with the BCG-admixed vaccine ( ATV/BCG ) . The mean value of delayed hypersensitivity skin reactions from ATV-NDV-treated patients was 18 mm for the first vaccination and 26 and 29 mm for the succeeding ones . Although the application of ATV-NDV was associated with only mild side effects , the ATV/BCG vaccine led to long-lasting ulcers and to more serious side effects . The 2-year survival rate obtained with ATV-NDV was 97.9 % , whereas the survival rate with ATV/BCG was 66.7 % . The mean survival of 661 patients from a historical control was 73.8 % . These data suggest that the type and quality of the tumor vaccine for ASI treatment is important . The findings with ATV-NDV necessitate corroboration in a prospect i ve , r and omized controlled study Active specific immunotherapy ( ASI ) is a strategy that attempts to boost the host 's immune response specifically against its own tumor . The purpose of this study was to investigate the effect of adjuvant ASI in patients with renal carcinoma In the area of cancer treatment , immunotherapy with vaccines has suffered 
    Output:
    
The combination of ASI immunotherapy and surgery was superior in prolonging the overall survival time and enhancing the recurrence-free survival rate compared with surgery alone