***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The MAGE gene is selectively expressed in cancer tissues such as melanoma or gastrointestinal carcinomas , whereas no expression is observed in normal tissues except testis . There are several reports of successful induction of HLA class I-restricted antitumor CTLs using MAGE peptides , and some clinical trials with these immunogenic peptides were reported as effective for some patients with malignant melanoma . However , there are no similar studies in gastrointestinal carcinomas , which are important neoplasms . Autologous dendritic cells ( DCs ) were generated ex vivo and were pulsed with MAGE-3 peptide , depending on the patient 's HLA haplotype ( HLA-A2 or A24 ) . Patients were immunized with DC pulsed with MAGE-3 peptide every 3 weeks at four times . Twelve patients with advanced gastrointestinal carcinoma ( six stomach , three esophagus , and three colon ) were treated , and no toxic side effects were observed . Peptide-specific CTL responses after vaccination were observed in four of eight patients .  Improvement in performance status was recognized in four patients . Tumor markers decreased in seven patients . In addition , minor tumor regressions evidence d by imaging studies were seen in three patients . These results suggested that DC vaccination with MAGE-3 peptide is a safe and promising approach in the treatment of gastrointestinal carcinomas Carcinoembryonic antigen ( CEA ) is expressed in a wide variety of adenocarcinomas , and it is well recognized that cancer patients are immunologically " tolerant " to CEA . The purpose of this study was to determine whether we could break immune tolerance to CEA by vaccinating patients with a monoclonal anti-idiotype antibody that is the internal image of CEA and to determine what impact this might have on patient survival . Twenty-four patients with advanced CEA-positive colorectal cancer who failed st and ard therapies except for two were entered into this Phase Ib trial . One patient was considered not assessable , because on the day of entering into the study , she was diagnosed with acute myelogenous leukemia . Patients were treated with 1 , 2 , or 4 mg of aluminum hydroxide-precipitated 3H1 anti-idiotype antibody every other week for four injections and then monthly until tumor progression was observed . Immunological monitoring included humoral and cellular idiotypic and CEA responses , and all patients were evaluated for toxicity , response , and survival . Hyperimmune sera from 17 of 23 patients demonstrated an anti-anti-idiotypic Ab3 response , and 13 of these responses were demonstrated to be true anti-CEA responses ( Ab1 ' ) . The antibody response was polyclonal , and 11 mediated antibody-dependent cellular cytotoxicity . Ten patients had idiotypic T-cell responses , and five had specific T-cell responses to CEA . None of the patients had objective clinical responses , but overall median survival for the 23 evaluable patients was 11.3 months , with 44 % 1-year survival ( 95 % confidence interval , 23 - 64 % ) . Toxicity was limited to local swelling and minimal pain . Anti-idiotype monoclonal antibody 3H1 that mimics CEA was able to break immune tolerance in the majority of treated patients . Overall survival of 11.3 months was comparable to other phase II data with advanced colorectal cancer patients treated with a variety of chemotherapy agents , including irinotecan , with considerably less toxicity . Although it is not clear that the vaccine itself had an impact on survival , this should be determined in a Phase III r and omized trial Most tumor-associated antigens represent self-proteins and as a result are poorly immunogenic due to immune tolerance . Here we show that tolerance to carcinoembryonic antigen ( CEA ) , which is overexpressed by the majority of lethal malignancies , can be reversed by immunization with a CEA-derived peptide . This peptide was altered to make it a more potent T cell antigen and loaded onto dendritic cells ( DCs ) for delivery as a cellular vaccine . Although DCs are rare in the blood , we found that treatment of advanced cancer patients with Flt3 lig and , a hematopoietic growth factor , exp and ed DCs 20-fold in vivo . Immunization with these antigen-loaded DCs induced CD8 cytotoxic T lymphocytes that recognized tumor cells expressing endogenous CEA . Staining with peptide-MHC tetramers demonstrated the expansion of CD8 T cells that recognize both the native and altered epitopes and possess an effector cytotoxic T lymphocyte phenotype ( CD45RA+CD27−CCR7− ) . After vaccination , two of 12 patients experienced dramatic tumor regression , one patient had a mixed response , and two had stable disease . Clinical response correlated with the expansion of CD8 tetramer+ T cells , confirming the role of CD8 T cells in this treatment strategy Despite an abundance of pre clinical data , relatively little is known regarding the efficacy of DNA vaccination in humans . Here , we present results from a dose-escalation clinical trial of a dual expression plasmid encoding carcinoembryonic antigen ( CEA ) and hepatitis B surface antigen ( HBsAg ) in 17 patients with metastatic colorectal carcinoma . CEA was selected as a prototypic tumor-associated self-antigen , and the HBsAg cDNA was included as a positive control for immune response to the DNA vaccine without relying upon breaking tolerance to a self-antigen . Groups of 3 patients received escalating single i.m . doses of the DNA vaccine at 0.1 , 0.3 , and 1.0 mg . Subsequent groups of 3 patients received three repetitive 0.3- or 1.0-mg doses at 3-week intervals . A final group of 2 patients received three repetitive 2.0 mg doses at 3-week intervals . Toxicity was limited to transient grade 1 injection site tenderness , fatigue , and creatine kinase elevations , each affecting a minority of patients in a non-dose-related manner . Repetitive dosing of the DNA vaccine induced HBsAg antibodies in 6 of 8 patients , with protective antibody levels achieved in four of these patients . CEA-specific antibody responses were not observed , but 4 of 17 patients developed lymphoproliferative responses to CEA after vaccination . No objective clinical responses to the DNA vaccine were observed among this population of patients with widely metastatic colorectal carcinoma . Nevertheless , this pilot trial has provided encouraging human immune response data in support of this vaccine technology We report here the adoptive transfer , to patients with metastatic melanoma , of highly selected tumor-reactive T cells directed against overexpressed self-derived differentiation antigens after a nonmyeloablative conditioning regimen . This approach result ed in the persistent clonal re population of T cells in those cancer patients , with the transferred cells proliferating in vivo , displaying functional activity , and trafficking to tumor sites . This led to regression of the patients ' metastatic melanoma as well as to the onset of autoimmune melanocyte destruction . This approach presents new possibilities for the treatment of patients with cancer as well as patients with human immunodeficiency virus – related acquired immunodeficiency syndrome and other infectious diseases 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 The purpose of this study was to determine the safety , toxicity , and antitumor immune response following S.C. immunizations with a mixture of irradiated , autologous tumor cells and autologous fibroblasts that were genetically modified to express the gene for interleukin 2 ( IL-2 ) in patients with colorectal carcinoma . Ten patients were treated with a fixed dose of tumor cells ( 10(7 ) ) and escalating doses of fibroblasts secreting IL-2 ( per 24 h ) : 100 units ( three patients ) , 200 units ( three patients ) , 400 units ( three patients ) , and 800 units ( one patient ) . Pre- and posttreatment peripheral blood mononuclear cells were evaluated for evidence of antitumor immune responses . Fatigue and /or flu-like symptoms were experienced by seven patients and delayed-type hypersensitivity-like skin reactions were observed at the sites of the second or subsequent vaccinations in five patients . Low frequencies of tumor cytotoxic T-cell precursors ( range , 1/190,000 - 1/1,320,000 peripheral blood mononuclear cells ) were detected prior to therapy in four of seven patients . There was a 5-fold increase following treatment in the frequency of tumor cytotoxic T-cell precursors in two of six evaluable patients . Some patients with colorectal cancer have low frequencies of tumor cytotoxic T-cell precursors that may be increased by this well-tolerated form of IL-2 gene therapy , which warrants continued clinical evaluation Purpose : We intranodally immunized metastatic colorectal carcinoma patients , who had failed st and ard chemotherapy , with dendritic cells ( DCs ) pulsed with HLA-A*0201- or HLA-A*2402-restricted carcinoembryonic antigen ( CEA ) peptides to evaluate the safety of this treatment and the immune response against CEA peptides before and after the treatment . Experimental Design : Six patients with the HLA-A*2402 genotype and 4 patients with the HLA-A*0201 genotype were enrolled . A single CEA peptide ( YLSGANLNL ) or two CEA peptides ( QYSWFVNGTF and TYACFVSNL ) were used for patients with the HLA-A*0201 or HLA-A*2402 genotype , respectively . Autologous DCs were generated by culturing adherent mononuclear cells with interleukin 4 and granulocyte macrophage colony-stimulating factor for 6 days . Maturation of DCs was then induced with tumor necrosis factor α for 40 h. Mature DCs were pulsed with appropriate CEA peptides for 2 h. After washing , 1 million peptide-pulsed DCs were injected into one inguinal lymph node under sonographic guidance . Each patient received four injections . Results : No grade II/III toxicity or autoimmunity was observed . An increase in the number of CEA-specific T cells after DC vaccination could be detected in 7 of 10 ( 70 % ) patients . Two ( 20 % ) patients had stable disease for at least 12 weeks . One of these 2 patients experienced a transient decrease in CEA levels during the treatment period and also had the most significant T-cell response against the immunizing CEA peptides . Conclusions : These results suggest that our vaccination procedure can generate or boost specific T-cell responses and may provide clinical benefit in certain cancer patients In most protocol s of peptide-based vaccination , no consideration has been paid to whether or not peptide-specific cytotoxic T-lymphocyte ( CTL ) precursors are pre-existent in cancer patients . Initiation of immune boosting through vaccination is better than that of immune priming to induce prompt and strong immunity . In this study , 10 human histocompatibility leukocyte antigen-A24 + patients with advanced colorectal carcinomas were treated with up to four peptides that had been positive for pre-vaccination measurement of peptide-specific CTL precursors in the circulation ( CTL precursor-oriented peptide vaccine ) . No severe adverse effect was observed , although local pain and fever of grade I or II were observed . Post-vaccination peripheral blood mononuclear cells ( P BMC s ) from five patients demonstrated an increased peptide-specific immune response to the peptides . Increased CTL response to cancer cells was detected in post-vaccination P BMC s of five patients . Antipeptide immunog 
    Output:
    
Pooled results of clinical trials reveal a very weak clinical response rate of < 1 % for active specific immunization procedures currently available for advanced colorectal cancer .