Technological advances in adoptive immunotherapy

Oelke, Mathias; Krueger, Christine; Schneck, Jonathan P.

doi:10.1358/dot.2005.41.1.875775

Cited by 12 publications

(12 citation statements)

References 39 publications

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“…Immobilization of HLA molecules onto beads or liposomes enhanced the expansion of antigen-specific T cells in mouse and human in vitro systems. Thus, different combinations of costimulatory signals and different amounts of HLA molecules were tested (reviewed in [57]).…”

Section: Novel Artificial Concepts Paving the Way To Kaapcmentioning

confidence: 99%

Killer Artificial Antigen-Presenting Cells: The Synthetic Embodiment of a ‘Guided Missile‘

Schütz¹,

Oelke

Schneck

et al. 2010

Immunotherapy

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At present, the treatment of T-cell-dependent autoimmune diseases relies exclusively on strategies leading to nonspecific suppression of the immune systems causing a substantial reduced ability to control concomitant infections or malignancies. Furthermore, long-term treatment with most drugs is accompanied by several serious adverse effects and does not consequently result in cure of the primary immunological malfunction. By contrast, antigen-specific immunotherapy offers the potential to achieve the highest therapeutic efficiency in accordance with minimal adverse effects. Therefore, several studies have been performed utilizing antigen-presenting cells specifically engineered to deplete allo-or antigen-specific T cells ('guided missiles'). Many of these strategies take advantage of the Fas/Fas ligand signaling pathway to efficiently induce antigen-presenting cellmediated apoptosis in targeted T cells. In this article, we discuss the advantages and shortcomings of a novel non-cell-based 'killer artificial antigen-presenting cell' strategy, developed to overcome obstacles related to current cell-based approaches for the treatment of T-cell-mediated autoimmunity. Keywordsantigen-presenting cell; apoptosis; artificial; killer artificial antigen-presenting cell; T cell Approximately 5% of the Western population are suffering from autoimmune diseases. Those individuals are in need of a long-term treatment to prevent organ damage and to reduce diseaserelated mortality. Still, the most common treatments of autoimmune diseases rely on corticosteroids as well as immunosuppressive drugs such as purine analogs, alkylating agents and calcineurin inhibitors [1]. Even though the use of such immuno suppressive drugs has greatly improved the prognosis of patients suffering from autoimmune diseases, these treatments do not provide a cure for the underlying immunological malfunction, and the ability to control concomitant infections or malignancies are frequently impaired. Furthermore, treatment does not result in prolonged periods of drug-free remissions. NIH Public Access Author ManuscriptImmunotherapy. Author manuscript; available in PMC 2011 May 1. Published in final edited form as:Immunotherapy. [4][5][6]. Therefore, there is still a necessity for the development of novel selective antigen-specific immunotherapies to further improve the treatment outcomes with reduced adverse effects at the same time.The idea of an antigen-specific therapy dates back to the 1970s and 1980s, when several groups discovered the existence of naturally occurring antigen-presenting cells (APCs) that suppressed peripheral T cells in an antigen-specific fashion. Such 'veto cells' presented autoantigens on their cell surface, facilitating elimination of T cells recognizing such antigens (reviewed in [7]). These findings were essentially amplified in the late 1980s and early 1990s through the discovery that natural APCs can be artificially modified to become 'artificial veto cells'. These cells were decorated with specific protein construc...

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Section: Novel Artificial Concepts Paving the Way To Kaapcmentioning

confidence: 99%

Killer Artificial Antigen-Presenting Cells: The Synthetic Embodiment of a ‘Guided Missile‘

Schütz¹,

Oelke

Schneck

et al. 2010

Immunotherapy

View full text Add to dashboard Cite

show abstract

“…Immunization regimens involving the use of ex vivo antigenpulsed or genetically engineered dendritic cells (DCs) to deliver and present antigens in vivo have produced promising experimental protective immunity against infectious diseases and cancers [50][51][52][53][54][55][56]. Antigen-pulsed DCs appear to possess the necessary antigenic, costimulatory and immunomodulatory features for inducing high levels of T-cell and antibody responses for optimal protective immunity.…”

Section: Cellular Vaccine Deliverymentioning

confidence: 99%

Combination vaccines: design strategies and future trends

Igietseme¹,

Eko²,

He³

et al. 2006

Expert Review of Vaccines

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“…This raises the possibility that spacing might be crucial for efficacy. In the HLA-A2-Igbased aAPC, the larger size of the complex [4] might fulfill the spacing requirements and facilitate its ability to stimulate T cells effectively.…”

Section: Mhc-class-ii-based Antigen-specific Aapcsmentioning

confidence: 99%

“…Therefore, many investigators have started to develop artificial (a)APCs. Advances in the development of aAPCs have been reviewed earlier [3,4], and the different technological advances in adoptive immunotherapy, including aAPCs and T-cell receptor (TCR) gene transfer, have been summarized [4]. Here, we discuss the molecular basis for T-cell activation and how this process affects aAPC design and their potential for usage in clinical applications.…”

Section: Introductionmentioning

confidence: 99%