Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG

Schadendorf, Dirk; Ugurel, Selma; Schuler‐Thurner, Beatrice; Nestle, Frank O.; Enk, Alexander H.; Bröcker, Eva‐Bettina; Grabbe, Stephan; Rittgen, Werner; Edler, Lutz; Sucker, Antje; Zimpfer-Rechner, C.; Berger, Thomas G.; Kamarashev, Jivko; Burg, Günter; Jonuleit, Helmut; Tüttenberg, Andrea; Becker, Jürgen C.; Keikavoussi, Petra; Kämpgen, Eckhart; Schuler, Gerold

doi:10.1093/annonc/mdj138

Cited by 411 publications

(262 citation statements)

References 21 publications

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“…Grade 3 or 4 treatment-related toxicity is extremely uncommon when DC vaccination is given as monotherapy (15). These data are confirmed by the available data from phase III trials where DC vaccination is compared with placebo (16)(17)(18)(19). Therefore, DC vaccination is considered safe and expected to preserve the quality of life in cancer patients.…”

Section: Safetymentioning

confidence: 77%

Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

Bol

Schreibelt

Gerritsen

et al. 2016

Clinical Cancer Research

288

238

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Dendritic cell (DC) vaccination in cancer patients aims to induce or augment an effective antitumor immune response against tumor antigens and was first explored in a clinical trial in the 1990s. More than two decades later, numerous clinical trials have been performed or are ongoing with a wide variety of DC subsets, culture protocols, and treatment regimens. The safety of DC vaccination and its ability to induce antitumor responses have clearly been established; however, although scattered patients with long-term benefit were reported, DC vaccines have not yet fulfilled their promise, perhaps mainly due to the lack of large-scale well-conducted phase II/III trials. To allow meaningful multicenter phase III trials, the production of DC vaccines should be standardized between centers which is now becoming feasible. To improve the efficacy of DC-based immunotherapy, it could be combined with other treatments.

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Section: Safetymentioning

confidence: 77%

Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

Bol

Schreibelt

Gerritsen

et al. 2016

Clinical Cancer Research

288

238

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“…Dendritic cell vaccines have been evaluated in phase I-III clinical trials for patients with various solid tumors such as melanoma, [18][19][20] prostate cancer, 21,22 renal cell carcinoma [23][24][25] and lymphoma. 26,27 Immunological and also clinical responses observed in these patients prompted researchers in the field to extend the concept of DC vaccination also to leukemia patients.…”

Section: Discussionmentioning

confidence: 99%

Vaccination of B-CLL patients with autologous dendritic cells can change the frequency of leukemia antigen-specific CD8+ T cells as well as CD4+CD25+FoxP3+ regulatory T cells toward an antileukemia response

et al. 2008

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Recently, we described that vaccination with allogeneic dendritic cells (DCs) pulsed with tumor cell lysate generated specific CD8 þ T cell response in patients with B-cell chronic lymphocytic leukemia (B-CLL). In the present study, the potential of autologous DCs pulsed ex vivo with tumor cell lysates to stimulate antitumor immunity in patients with B-CLL in early stages was evaluated. Twelve patients at clinical stage 0-2 as per Rai were vaccinated intradermally up to eight times with a mean number of 7.4 Â 10 6 DCs pulsed with B-CLL cell lysate. We observed a decrease of peripheral blood leukocytes and CD19 þ /CD5 þ leukemic cells in five patients, three patients showed a stable disease and four patients progressed despite DC vaccination. A significant increase of specific cytotoxic CD8 þ T lymphocytes against the leukemia-associated antigens RHAMM or fibromodulin was detected in four patients after DC vaccination. In patients with a clinical response, an increase of interleukin 12 (IL-12) serum levels and a decrease of the frequency of CD4 þ CD25 þ FOXP3 þ T regulatory cells were observed. Taken together, the study demonstrated that vaccination with autologous DC in CLL patients is feasible and safe. Immunological and to some extend hematological responses could be noted, justifying further investigation on this immunotherapeutical approach.

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“…As vaccinations with moDCs have rarely induced clinical responses, over the past years attempts to use these naturally occurring DC subsets in clinical trials were intensified. [84][85][86][87] For the clinical use, both subsets can be isolated from peripheral blood using their respective markers. In addition, myeloid DCs can also be cultured in vitro from CD34+ cells.…”

Section: Selection Of DC Source and Typementioning

confidence: 99%

Minor histocompatibility Ags: identification strategies, clinical results and translational perspectives

Oostvogels

Lokhorst

Mutis

2015

Bone Marrow Transplant

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Allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusion are effective treatment modalities for various hematological malignancies. Their therapeutic effect, the graft-versus-tumor (GvT) effect, is based mainly on an alloimmune response of donor T cells directed at tumor cells, in which differences in the expression of minor histocompatibility Ags (mHags) on the cells of the patient and donor have a crucial role. However, these differences are also responsible for induction of sometimes detrimental GvHD. As relapse and development of GvHD pose major threats for a large proportion of allotransplanted patients, additional therapeutic strategies are required. To augment the GvT response without increasing the risk of GvHD, specific mHagdirected immunotherapeutic strategies have been developed. Over the past years, much effort has been put into the identification of therapeutically relevant mHags to enable these strategies for a substantial proportion of patients. Currently, the concept of mHag-directed immunotherapy is tested in clinical trials on feasibility, safety and efficacy. In this review, we will summarize the recent developments in mHag identification and the clinical data on mHag-specific immune responses and mHag-directed therapies in patients with hematological malignancies. Finally, we will outline the current challenges and future prospectives in the field.

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Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG

Cited by 411 publications

References 21 publications

Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

Dendritic Cell–Based Immunotherapy: State of the Art and Beyond

Vaccination of B-CLL patients with autologous dendritic cells can change the frequency of leukemia antigen-specific CD8+ T cells as well as CD4+CD25+FoxP3+ regulatory T cells toward an antileukemia response

Minor histocompatibility Ags: identification strategies, clinical results and translational perspectives

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