Employing the immunological synapse in AML: Development of leukemic dendritic cells for active specific immunization

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

doi:10.1016/j.imbio.2005.05.019

Cited by 12 publications

(9 citation statements)

References 73 publications

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“…In a phase I pilot study on chronic myelogenous leukemia -derived dendritic cell vaccination in the advanced-stage disease, delayed type hypersensitivity responses representing autologous chronic myelogenous leukemia -specific T-cell responses were detected (27) However, clinical dendritic cell vaccination studies have, until now, shown limited success (18,19). Targeting costimulatory pathways that are known to prolong T-cell survival and function could be instrumental to potentiate immune responses elicited by tumor-specific dendritic cells (28).…”

Section: Discussionmentioning

confidence: 99%

Leukemia-Specific T-Cell Reactivity Induced by Leukemic Dendritic Cells Is Augmented by 4-1BB Targeting

Houtenbos¹,

Westers²,

Dijkhuis³

et al. 2007

Clinical Cancer Research

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Purpose: Acute myelogenous leukemia (AML) blasts are able to differentiate into leukemiaderived dendritic cells (AML-DC), thereby enabling efficient presentation of known and unknown leukemic antigens. Advances in culture techniques and AML-DC characterization justify clinical application. However, additional measures are likely needed to potentiate vaccines and overcome the intrinsic tolerant state of the patients' immune system. Engagement of the costimulatory molecule 4-1BB can break immunologic tolerance and increase CTL responses. In this study, we examined the role of the 4-1BB ligand (4-1BBL) onT-cell responses induced by AML-DC. Experimental Design: In allogeneic and autologous cocultures of T cells and AML-DC, the effect of the addition of 4-1BBL on T-cell proliferation, T-cell subpopulations, and T-cell function was determined. Results: Addition of 4-1BBL to cocultures of AML-DC and Tcells induced a preferential increase in the proliferation of CD8 + T cells. Increased differentiation into effector and central memory populations was observed in both CD4 + and CD8 + T cells in the presence of 4-1BBL. AML-DC induce a T helper 1 response, characterized by high IFN-g production, which is significantly increased by targeting 4-1BB. T cells primed in the presence of 4-1BBL show specificity for the leukemia-associated antigen Wilms' tumor 1, whereas cytotoxicity assays with leukemic blast targets showed the cytolytic potential of Tcells primed in the presence of 4-1BBL. Conclusion: We conclude that 4-1BBL is an effective adjuvant to enhance T-cell responses elicited by AML-DC.

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Section: Discussionmentioning

confidence: 99%

Leukemia-Specific T-Cell Reactivity Induced by Leukemic Dendritic Cells Is Augmented by 4-1BB Targeting

Houtenbos¹,

Westers²,

Dijkhuis³

et al. 2007

Clinical Cancer Research

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“…New approaches are needed to warrant use of DC vaccines in treating leukemia (113), and more strategies are required to sensitize residual leukemic cells. This aspect warrants further investigation in order to increase the immune stimulatory effect of leukemic DCs (114). Areas that are ripe for study are the components needed to produce DCs for therapy, including their culture and cytokine profile, antigen loading and delivery, and the potential for combination of DC-based immunomodulatory strategies (115).…”

Section: Leukemia-derived Dcs For Clinical Use and Results Of Clinicamentioning

confidence: 99%

The characterization and role of leukemia cell-derived dendritic cells in immunotherapy for leukemic diseases

Yuan

Song

Jiang

2012

Intractable Rare Dis Res

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“…The first report on successful generating of AML-DCs in vitro by Santiago-Schwartz and et al, opened a promising way toward a simple DC generation method from available blasts for future DC immunotherapy in AML patients [35,38]. AML-DCs can differentiate from blasts in relapse phase and induce anti-leukemic T-cell responses [39,40]. These cells can be successfully generated and regain the stimulatory capacity of mature monocyte-derived DCs (i.e.…”

Section: Possibility Of Generating Blast-derived Dcsmentioning

confidence: 99%

Effective Dendritic Cell-based Immunotherapeutic Vaccines for Acute Myeloid Leukemia (AML)

Nourizadeh

Hadjati

2014

vacres

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Employing the immunological synapse in AML: Development of leukemic dendritic cells for active specific immunization

Cited by 12 publications

References 73 publications

Leukemia-Specific T-Cell Reactivity Induced by Leukemic Dendritic Cells Is Augmented by 4-1BB Targeting

Leukemia-Specific T-Cell Reactivity Induced by Leukemic Dendritic Cells Is Augmented by 4-1BB Targeting

The characterization and role of leukemia cell-derived dendritic cells in immunotherapy for leukemic diseases

Effective Dendritic Cell-based Immunotherapeutic Vaccines for Acute Myeloid Leukemia (AML)

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