Vaccination of patients with cutaneous T-cell lymphoma using intranodal injection of autologous tumor-lysate–pulsed dendritic cells

Maier, Tanja; Tun-Kyi, Adrian; Tassis, Anatoli; Jungius, Karl-Peter; Burg, G.; Dummer, Reinhard; Nestle, Frank O.

doi:10.1182/blood-2002-08-2455

Cited by 126 publications

(78 citation statements)

References 36 publications

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“…So far, only a limited rate of objective tumor regressions has been observed in clinical studies [3,5,9,14,25,27,44]. One reason for the discrepancy between the outcomes as seen in the pre-clinical feasibility assays with respect to the true clinical responses could be that most pre-clinical in vitro tumor models that evaluate direct cytotoxicity of DCs have been performed on either cancer cell lines or mice models [22,30,31,41,52].…”

Section: Discussionmentioning

confidence: 99%

“…DiVerent antigens have been used and tested for their immunopotency. These include synthetic peptides [16,35,45], tumor lysates [27] and cDNA or RNA encoding for speciWc tumor-associated antigens as well as total tumor mRNA [20,29,33,49,51]. The introduction of autologous total tumor RNA as an antigen source for loading DCs has several advantages.…”

Section: Introductionmentioning

confidence: 99%

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An ex vivo readout for evaluation of dendritic cell-induced autologous cytotoxic T lymphocyte responses against esophageal cancer

Milano

Rygiel

Buttar

et al. 2007

Cancer Immunol Immunother

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Esophageal cancer is a highly malignant disease that despite surgery and adjuvant therapies has an extremely poor outcome. Dendritic cell (DC) immunotherapy as a novel promising strategy could be an alternative for treating this malignancy. EVective DC-mediated immune responses can be achieved by raising cytotoxic T lymphocyte (CTL) response against multiple antigens through loading DCs with total tumor RNA. However, the eYcacy of this strategy Wrst needs to be evaluated in a preclinical setting. The aim of the study was to set up an ex vivo autologous human readout assay for assessing the eVects of DC-mediated cytotoxic responses, using total tumor RNA as an antigen load. Biopsy specimens of seven esophageal cancer patients were used to establish primary cultures of normal and cancer cells and to obtain autologous RNA for loading DCs. Mature DCs loaded with either normal or tumor RNA were obtained and subsequently used to raise various lymphocytes populations. Apoptosis levels of the autologous cultures were measured before and after incubating the cultures with the diVerent lymphocytes populations. The mean apoptosis levels in the tumor cell cultures, induced by lymphocytes instructed by DCs loaded with tumor RNA, signiWcantly increased with 15.6% §2.9 SEM (range 3.4-24.5%, t-test, P < 0.05). Incubation of the normal cultures with the lymphocytes populations showed a mean non-signiWcant increase in apoptosis of 0.4% §3.4 SEM (range ¡13.9 to 9.8%, t-test, P = 0.7). Here, we introduce a practical, patient-speciWc autologous readout assay for pre-clinical testing of DC-mediated cytotoxic responses. Additionally, we demonstrated that the use of autologous tumor RNA as a strategy for raising cytotoxic responses against multiple tumor antigens could be eVective for treating esophageal cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An ex vivo readout for evaluation of dendritic cell-induced autologous cytotoxic T lymphocyte responses against esophageal cancer

Milano

Rygiel

Buttar

et al. 2007

Cancer Immunol Immunother

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“…Clinical trials using antigen-loaded dendritic cells (DC) as APC have already been tested in Phase II and III clinical trials for the treatment of various tumors [1][2][3]. Recently, RNA-loaded DC were used to induce T cell responses against specific tumor rejection antigens [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Efficient antitumor immunity in a murine colorectal cancer model induced by CEA RNA‐electroporated B cells

et al. 2008

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RNA electroporation as a gene delivery method is more feasible and safer as compared with viral vectors. RNA-loaded dendritic cells (DC) have been used to induce T cell responses against tumor rejection antigens and B cells can also act as antigen-presenting cells for cellular vaccines. In this study, we compared B cells and DC, after electroporation with carcinoembryonic antigen (CEA) RNA, for their capacity to generate cytotoxic T lymphocytes and antitumor immunity. Vaccination using these B cells induced levels of IFN-c-secreting T cells and cytotoxic T cells comparable to those induced by DC. Intravenous administration was the optimum route for the B cell vaccine, while subcutaneous administration was the optimum route for the DC vaccine. The B cell vaccine predominantly generated CEA-specific CD4 + T cells, whereas the DC vaccine generated CD8 + T cells. Moreover, the B cell vaccine induced higher levels of anti-CEA antibodies than the DC vaccine. A heterogeneous prime-boost using B cells and DC failed to show any synergistic effects; however, the B cell vaccine did inhibit tumor growth and prolonged survival to a similar extent as the DC vaccine. Such RNA-electroporated B cells may prove useful as cellular tumor vaccines with potential clinical application.

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“…Immunizing with dendritic cells (DCs) loaded with whole-tumor-cell preparations also bears in theory the potential risk of inducing autoimmunity against self-antigens of the tumor. However, such an approach seems to be safe and not associated with autoimmunity as for example for cutaneous T lymphoma [30] or for glioma [31]. The first clinical trial using a DC-based cancer vaccine for glioma patients consisting in DCs pulsed with acid-eluted peptides from cultured autologous Editorial tumor cells and injected intradermally into the deltoid region three-times biweekly also showed no significant side effect and autoimmune syndromes [32].…”

Section: Damp Regulation Via the Cd24-siglecs Pathway: An Explanationmentioning

confidence: 99%

Danger signals in tumor cells: a risk factor for autoimmune disease?

Schirrmacher

Fournier

2010

Expert Review of Vaccines

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Vaccination of patients with cutaneous T-cell lymphoma using intranodal injection of autologous tumor-lysate–pulsed dendritic cells

Cited by 126 publications

References 36 publications

An ex vivo readout for evaluation of dendritic cell-induced autologous cytotoxic T lymphocyte responses against esophageal cancer

An ex vivo readout for evaluation of dendritic cell-induced autologous cytotoxic T lymphocyte responses against esophageal cancer

Efficient antitumor immunity in a murine colorectal cancer model induced by CEA RNA‐electroporated B cells

Danger signals in tumor cells: a risk factor for autoimmune disease?

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