***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: We have developed an individualized melanoma vaccine based on transfection of autologous dendritic cells ( DCs ) with autologous tumor-mRNA . Dendritic cells loaded with complete tumor-mRNA may generate an immune response against a broad repertoire of antigens , including unique patient-specific antigens . The purpose of the present phase I/II trial was to evaluate the feasibility and safety of the vaccine , and the ability of the DCs to elicit T-cell responses in melanoma patients . Further , we compared intradermal ( i.d . ) and intranodal ( i.n . ) vaccine administration .  Twenty-two patients with advanced malignant melanoma were included , each receiving four weekly vaccines . Monocyte-derived DCs were transfected with tumor-mRNA by electroporation , matured and cryopreserved . We obtained successful vaccine production for all patients elected . No serious adverse effects were observed . A vaccine-specific immune response was demonstrated in 9/19 patients evaluable by T-cell assays ( T-cell proliferation/interferon-γ ELISPOT ) and in 8/18 patients evaluable by delayed-type hypersensitivity ( DTH ) reaction . The response was demonstrated in 7/10 patients vaccinated intradermally and in 3/12 patients vaccinated intranodally . We conclude that immuno-gene-therapy with the described DC-vaccine is feasible and safe , and that the vaccine can elicit in vivo T-cell responses against antigens encoded by the transfected tumor-mRNA . The response rates do not suggest an advantage in applying i.n . vaccination Adoptive immunotherapy with anti-CD3-exp and ed lymphocytes from lymph nodes draining alloantigen gene-modified autologous tumor vaccines is an effective treatment of poorly immunogenic murine tumors . This phase I/II study was performed to determine the feasibility and toxicity of combining ex vivo gene transfer of autologous tumor cells and adoptive immunotherapy with anti-CD3-exp and ed tumor vaccine draining lymph node lymphocytes ( TVDLN ) in patients with metastatic melanoma and renal cell cancer ( RCC ) . To facilitate the generation of tumor-specific lymphocytes in the TVDLN , autologous tumor cells were modified by gene transfer ex vivo to express the alloantigen HLA-B7 , a modification that has the potential to enhance the immunogenicity of the tumor cells . After vaccination with gene-modified tumor cells , patients ' lymph nodes were harvested ; TVDLN lymphocytes were activated and exp and ed ex vivo with anti-CD3 and interleukin-2 ( IL-2 ) , and adoptively transferred to patients in combination with systemic IL-2 .  Twenty patients , nine with melanoma and 11 with RCC were treated . Tumor was harvested successfully in all 20 patients . Ex vivo gene transfer was performed using lipofection with a lipid : DNA plasmid complex containing the genes for HLA-B7 and & bgr;2-microglobulin . The mean expression of HLA-B7 by autologous tumor cells after gene transfer was 4.53 % ( range 0.3%–12.1 % ) . Lymph nodes were harvested from all 20 patients with a mean of 53 × 107 and 60 × 107 cells obtained from the gene-modified and unmodified tumor vaccine sites , respectively . Successful expansion of adequate TVDLN was accomplished in 19 of 20 harvests of unmodified vaccines and in 18 of 20 gene-modified vaccines . No major toxicities were noted after vaccination with autologous tumor cells or adoptive transfer of ex vivo activated TVDLN lymphocytes . Typical IL-2-related toxicities were observed in all patients . No objective tumor regressions were observed . MHC class I restricted , tumor-specific cytokine secretion was observed in lymphocytes from TVDLN and the peripheral blood of vaccinated patients PURPOSE To assess the antitumor activity of vitespen ( autologous , tumor- derived heat shock protein gp96 peptide complexes ) by determining whether patients with stage IV melanoma treated with vitespen  experienced longer overall survival than patients treated with physician 's choice . PATIENTS AND METHODS Patients ( N = 322 ) were r and omly assigned 2:1 to receive  vitespen or physician 's choice ( PC ) of a treatment containing one or more of the following : dacarbazine , temozolomide , interleukin-2 , or complete tumor resection . This open-label trial was conducted at 71 centers worldwide . Patients were monitored for safety and overall survival . RESULTS Therapy with vitespen is devoid of significant toxicity . Patients r and omly assigned to the vitespen arm received variable number of injections ( range , 0 to 87 ; median , 6 ) in part because of the autologous nature of vitespen therapy . Intention-to-treat analysis showed that overall survival in the vitespen arm is statistically indistinguishable from that in the PC arm . Exploratory l and mark analyses show that patients in the M1a and M1b substages receiving a larger number of vitespen immunizations survived longer than those receiving fewer such treatments . Such difference was not detected for substage M1c patients . CONCLUSION These results are consistent with the immunologic mechanism of action of vitespen , indicating delayed onset of clinical activity after exposure to the vaccine . The results suggest patients with M1a and M1b disease who are able to receive 10 or more doses of vitespen as the c and i date population for a confirmatory study Dendritic cell (DC)‐based therapy has proved to be effective in patients with a variety of malignancies . However , an optimal immunization protocol using DCs and the best means for delivering antigens has not yet been described . In this study , 20 patients with malignant melanoma in stages III or IV were vaccinated with autologous DCs pulsed with a melanoma cell lysate , alone ( n = 13 ) or in combination with low doses of subcutaneous ( s.c . ) interleukin (IL)‐2 injections ( n = 7 ) , to assess toxicity , immunological and clinical responses . Monocyte‐derived DCs were morphological , phenotypic and functionally characterized in vitro . Peripheral blood mononuclear cells ( P BMC ) , harvested from patients either prior to and after the treatment , were analysed using enzyme‐linked immunosorbent spot ( ELISPOT ) . After vaccination , 50 % of the patients tested ( seven of 13 ) from the first group and ( three of seven ) from the second , showed an increase in interferon (IFN)‐γ production in response to allogeneic melanoma cell lines but not to controls . Four of five tested human leucocyte antigen (HLA)‐A2 + patients with anti‐melanoma activity also showed specific T cell responses against peptides derived from melanoma‐associated antigens . Delayed type IV hypersensitivity reaction ( DTH ) against melanoma cell lysate was observed in six of 13 patients from the group treated with DC vaccines only and four of seven from the group treated with the combination of DCs and IL‐2 . Significant correlations were found between DTH‐positive responses against tumour lysate and both disease stability and post‐vaccination survival on the stage IV patients . There were no toxicities associated with the vaccines or evidence of autoimmunity including vitiligo . Furthermore , no significant enhancement was observed as a result of combining DC vaccination with IL‐2 . Our data suggest that autologous DCs pulsed with tumour lysate may provide a st and ardized and widely applicable source of melanoma specific antigens for clinical use . It is safe and causes no significant side effects and has been demonstrated to be partially efficient at triggering effective anti‐melanoma immunity Vaccination against tumor antigens has been shown to be a safe and efficacious prophylactic and therapeutic antitumor treatment in many animal models . Clinical studies in humans indicate that specific immunotherapy can also result in clinical benefits . The active pharmaceutical ingredient in such vaccines can be DNA , RNA , protein , or peptide and can be administered naked , encapsulated , or after delivery in vitro into cells that are then adoptively transferred . One of the easiest , most versatile and theoretically safest technologies relies on the direct injection of naked messenger RNA ( mRNA ) that code for tumor antigens . We and others have shown in mice that intradermal application of naked mRNA results in protein expression and the development of an immune response . We used this protocol to vaccinate 15 melanoma patients . For each patient a growing metastasis was removed , total RNA was extracted , reverse-transcribed , amplified , and cloned . Libraries of cDNA were transcribed to produce unlimited amounts of copy mRNA . Autologous preparations were applied intradermally in combination with granulocyte macrophage colony-stimulating factor as adjuvant . We demonstrate here that such treatment is feasible and safe ( phase 1 criteria ) . Furthermore , an increase in antitumor humoral immune response was seen in some patients . However , a demonstration of clinical effectiveness of direct injection of copy mRNA for antitumor immunotherapy was not shown in this study and must be evaluated in subsequent trials Advanced metastatic melanoma is incurable by st and ard treatments , but occasionally responds to immunotherapy . Recent trials using dendritic cells ( DC ) as a cellular adjuvant have concentrated on defined peptides as the source of antigens , and rely on foreign proteins as a source of help to generate a cell-mediated immune response . This approach limits patient accrual , because currently defined , non-mutated epitopes are restricted by a small number of human leucocyte antigens . It also fails to take advantage of mutated epitopes peculiar to the patient 's own tumour , and of CD4 + T lymphocytes as potential effectors of anti-tumour immunity . We therefore sought to determine whether a fully autologous DC vaccine is feasible , and of therapeutic benefit . Patients with American Joint Cancer Committee stage IV melanoma were treated with a fully autologous immunotherapy consisting of monocyte-derived DC , matured after culture with irradiated tumour cells . Of 19 patients enrolled into the trial , sufficient tumour was available to make treatments for 17 . Of these , 12 received a complete priming phase of six cycles of either 0.9 × 106 or 5 × 106 DC/intradermal injection , at 2-weekly intervals . Where possible , treatment continued with the lower dose at 6-weekly intervals . The remaining five patients could not complete priming , due to progressive disease . Three of the 12 patients who completed priming have durable complete responses ( average duration 35 months+ ) , three had partial responses , and the remaining six had progressive disease ( WHO criteria ) . Disease regression was not correlated with dose or with the development of delayed type hypersensitivity responses to intradermal challenge with irradiated , autologous tumour . However , plasma S-100B levels prior to the commencement of treatment correlated with objective clinical response ( P=0.05 ) and survival ( log rank P<0.001 ) . The treatment had minimal side-effects and was well tolerated by all patients . Mature , monocyte-derived DC preparations exposed to appropriate tumour antigen sources can be reliably produced for patients with advanced metastatic melanoma , and in a subset of those patients with lower volume disease their repeated administration results in durable complete responses Background In the present study , we have examined whether treatment of patients with metastatic melanoma with matured dendritic cell ( DC ) vaccines with or without low dose IL-2 may improve treatment outcomes . Methods Sixteen patients received DC vaccines ( DCs ) sensitized with autologous melanoma lysates and 18 patients received DCs sensitized with peptides from gp100 , MART-1 , tyrosinase , MAGE-3.A2 , MAGE-A10 and NA17 . IL-2 was given subcutaneously ( sc ) at 1 MU/m2 on the second day after each injection for 5–14 days in half of each group . DCs were given by intranodal injection . Results There were 2 partial responses ( PR ) and 3 with stable disease ( SD ) in the nine patients receiving DCs + peptides + IL-2 , and 1 PR and 1 SD in nine patients treated with DCs + peptides without IL-2 . There were only two patients with SD in the group receiving DCs + autologous lysates and no IL-2 . Median overall survival for all patients was very good at 18.5 months but this was most probably due to selection of a favourable group of patients for the study . There was no significant difference in survival between the groups by log rank analysis . Treatment was not associated with significant side effects . The quality and yield of the DCs in the preparations were generally good . Conclusions We conclude that mature DC preparations may be superior to immature DC preparations for presentation of melanoma peptides and that IL-2 may increase clinical responses to the DCs plus peptides . However , in our view the low response rates do not justify the cost and complexity of this treatment approach PURPOSE The curative effect of surgery in certain patients with metastatic melanoma suggests the presence of endogenous antitumor responses . Because melanoma is immunogenic , we investigated whether a therapeutic cancer vaccine called Canvaxin ( CancerVax Corporation , Carlsbad , CA ) could enhance antitumor immune responses and thereby prolong survival . PATIENTS AND METHODS Of 263 patients who underwent complete resection of American Joint Committee on Cancer stage IV melanoma , 150 received postoperative 
    Output:
    
Overall , a melanoma-specific immune response predicted longer overall survival , although no evidence was found that vaccine therapy provides better overall disease control or overall survival compared with other treatments