Feasibility of clinical dendritic cell vaccination in acute myeloid leukemia

Houtenbos, Ilse; Westers, Theresia M.; Ossenkoppele, Gert J.; Loosdrecht, Arjan A. van de

doi:10.1016/j.imbio.2006.05.013

Cited by 25 publications

(12 citation statements)

References 57 publications

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“…[41][42][43][44][45][46] In particular, we demonstrated that AML cells favor the de novo emergence of a population of Tregs through the aberrant over-expression of IDO1 protein. 14 In the present study, we show that IDO1-expressing AML-DC expand, in vitro, a population of CD4 © F e r r a t a S t o r t i F o u n d a t i o n immunotherapy, 19 our results have some clinical implications. The initiation of a T-cell immune response depends strictly on the balance between different activating or inhibiting pathways, which act during DC/T cell encounters.…”

Section: Cd25supporting

confidence: 62%

“…19 The rationale relies on the concept that ex-vivo differentiation of AML blasts to DC has the advantage of obtaining antigen-presenting cells in the absence of in-vivo acting immunosuppressive factors. However, we previously demonstrated that a significant portion of AML-DC have impaired IL-12 production and …”

Section: Discussionmentioning

confidence: 99%

“…[15][16][17][18] Thus, AML-DC have been proposed for use as a cellular vaccine in leukemia patients for the treatment of minimal residual disease. 19 However, we previously demonstrated that AML-DC are not fully competent to revert T-cell impairment induced by the leukemic microenvironment, 20 and it remains to be elucidated whether AML-DC retain some intrinsic tolerogenic features, including the capacity of inducing Tregs. To this end, in the present study, we tested the expression of IDO1 by AML-DC and the functional role of this enzyme in the development of Treg cells.…”

Section: Introductionmentioning

confidence: 99%

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Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells

Curti¹,

Trabanelli²,

Onofri³

et al. 2010

Haematologica

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The online version of this article has a Supplementary Appendix. BackgroundThe immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients with acute myeloid leukemia, resulting in the inhibition of T-cell proliferation and the induction of regulatory T cells. Acute myeloid leukemia cells can be differentiated into dendritic cells, which have increased immunogenicity and have been proposed as vaccines against leukemia. Design and MethodsLeukemic dendritic cells were generated from acute myeloid leukemia cells and used as stimulators in functional assays, including the induction of regulatory T cells. Indoleamine 2,3-dioxygenase expression in leukemic dendritic cells was evaluated at molecular, protein and enzymatic levels. ResultsWe demonstrate that, after differentiation into dendritic cells, both indoleamine 2,3-dioxygenase-negative and indoleamine 2,3-dioxygenase-positive acute myeloid leukemia samples show induction and up-regulation of indoleamine 2,3-dioxygenase gene and protein, respectively. Indoleamine 2,3-dioxygenase-positive acute myeloid leukemia dendritic cells catabolize tryptophan into kynurenine metabolite and inhibit T-cell proliferation through an indoleamine 2,3-dioxygenase-dependent mechanism. Moreover, indoleamine 2,3-dioxygenase-positive leukemic dendritic cells increase the number of allogeneic and autologous CD4 ConclusionsThese data identify indoleamine 2,3-dioxygenase-mediated catabolism as a tolerogenic mechanism exerted by leukemic dendritic cells and have clinical implications for the use of these cells for active immunotherapy of leukemia.Key words: acute myeloid leukemia, dendritic cells, T regulatory cells, immunotherapy, indoleamine 2,3-dioxygenase.Citation: Curti A, Trabanelli S, Onofri C, Aluigi M, Salvestrini V, Ocadlikova D, Evangelisti C, Rutella S, De Cristofaro R, Ottaviani E, Baccarani M, and Lemoli RM. Indoleamine 2, leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells. Haematologica 2010;95(12):2022-2030. doi:10.3324/haematol.2010 This is an open-access paper. © F e r r a t a S t o r t i F o u n d a t i o n Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells

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Section: Cd25supporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells

Curti¹,

Trabanelli²,

Onofri³

et al. 2010

Haematologica

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“…4,5 In spite of their potency, the application of ex vivo DCs is so far limited by their availability. Growth of ex vivo DCs is both labour and resource intensive.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic nanoworms: towards novel synthetic dendritic cells for immunotherapy

et al. 2013

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A new class of antibody-functionalized, semi-flexible and filamentous polymers (diameter 5-10 nm, length $200 nm) with a controlled persistence length, a high degree of stereoregularity and the potential for multiple simultaneous receptor interactions has been developed. We have decorated these highly controlled, semi-stiff polymers with T cell activating anti-CD3 antibodies and analyzed their application potential as simple synthetic mimics of dendritic cells (sDCs). Our sDCs do not only activate T cells at significantly lower concentrations than free antibodies or rigid sphere-like counterparts (PLGA particles) but also induce a more robust T cell response. Our novel design further yields sDCs that are biocompatible and non-toxic. The observed increased efficacy highlights the importance of architectural flexibility and multivalency for modulating T cell response and cellular function in general.

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“…The AML-derived cell line MUTZ-3, an immortalized equivalent of CD34(+) Dendritic cells precursor cells, is under investigation for vaccination purposes. [46] Clinical relevant responses to Dendritic cells based immunotherapy are likely to only occur in non-end-stage patients [47]. Induction of antigenspecific T-cell tolerance in the thymus and its maintenance in the periphery is crucial for the prevention of autoimmunity [48].…”

Section: Immune Stimulatory Capacity Of Dendritic Cellsmentioning

confidence: 99%

Immunotherapy and Therapeutic antibodies

Gupta¹,

A²,

K³

et al. 2009

Int J of Biot Appl

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Abstract-Treatment of disorders through immune manipulation of the host has come a long way in the last decades and has broadened its applications from infectious diseases to control of allograft rejection, induction of tolerance for the treatment of autoimmunity and break of tolerance to induce cancer rejection. Immunotherapy, biological response modifier therapy or biotherapy uses the immune system to fight disease like cancer. The potentials of immunotherapy are many. The objective of this review article is to increase awareness of contemporary immunologic therapies and recent advances in immunotherapy.

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Feasibility of clinical dendritic cell vaccination in acute myeloid leukemia

Cited by 25 publications

References 57 publications

Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells

Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells

Therapeutic nanoworms: towards novel synthetic dendritic cells for immunotherapy

Immunotherapy and Therapeutic antibodies

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