Expansion of Polyfunctional HIV-Specific T Cells upon Stimulation with mRNA Electroporated Dendritic Cells in the Presence of Immunomodulatory Drugs

Keersmaecker, Brenda De; Allard, Sabine; Lacor, Patrick; Schots, Rik; Thielemans, Kris; Aerts, Joeri L.

doi:10.1128/jvi.00472-12

Cited by 15 publications

(12 citation statements)

References 52 publications

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“…The high clinical activity of the compound depends at least in part on its potent immunoactivating properties. Lenalidomide has been reported to enhance activation and antigen-specific expansion of CD8 + T cells [22][23][24] and to increase the breadth of antigen-specific CD8 + T cell responses [22]. Although lenalidomide was reported to have no impact on NK cell frequencies, it was associated with enhanced NK cell activity [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Treatment with lenalidomide induces immunoactivating and counter-regulatory immunosuppressive changes in myeloma patients

Busch

Zeh

Janzen

et al. 2014

Clinical and Experimental Immunology

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SummaryLenalidomide activates the immune system, but the exact immunomodulatory mechanisms of lenalidomide in vivo are poorly defined. In an observational study we assessed the impact of lenalidomide on different populations of immune cells in multiple myeloma patients. Lenalidomide therapy was associated with increased amounts of a CD8 + T cell subset, phenotypically staged between classical central memory T cells (TCM) and effector memory T cells (TEM), consequently termed TCM/TEM. The moderate expression of perforin/granzyme and phenotypical profile of these cells identifies them as not yet terminally differentiated, which makes them promising candidates for the anti-tumour response. In addition, lenalidomide-treated patients showed higher abundance of CD14 + myeloid cells co-expressing CD15. This population was able to inhibit both CD4 + and CD8 + T cell proliferation in vitro and could thus be defined as a so far undescribed novel myeloid-derived suppressor cell (MDSC) subtype. We observed a striking correlation between levels of TCM/TEM, mature regulatory T cells (Tregs) and CD14 + CD15 + MDSCs. In summary, lenalidomide induces both activating and inhibitory components of the immune system, indicating the existence of potential counter-regulatory mechanisms. These findings provide new insights into the immunomodulatory action of lenalidomide.

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Section: Introductionmentioning

confidence: 99%

Treatment with lenalidomide induces immunoactivating and counter-regulatory immunosuppressive changes in myeloma patients

Busch

Zeh

Janzen

et al. 2014

Clinical and Experimental Immunology

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“…72,73 Current efforts to use gene transfer for prevention or treatment of viral infections are focused on AIDS. [74][75][76] The goal in these efforts is to introduce 1 or more genetic elements into autologous hematopoietic stem cells that are then used to reconstitute the hematopoietic system of the AIDS patient to create a population of HIV-resistant T cells. Several studies have focused on the knockdown or knockout of the CCR5 gene as it encodes a potent coreceptor for HIV infection.…”

Section: Viral Infectionsmentioning

confidence: 99%

Development of gene therapy for blood disorders: an update

Nienhuis

2013

Blood

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This review addresses the current status of gene therapy for immunodeficiencies, chronic granulomatous disease, suicide gene therapy for graft-versus-host disease, viral infections, malignant hematologic disorders, hemophilia, and the hemoglobin disorders. New developments in vector design have fostered improved expression as well as enhanced safety, particularly of integrating retroviral vectors. Several immunodeficiencies have been treated successfully by stem cell–targeted, retroviral-mediated gene transfer with reconstitution of the immune system following infusion of the transduced cells. In a trial for hemophilia B, long-term expression of human FIX has been observed following adeno-associated viral vector–mediated gene transfer into the liver. This approach should be successful in treating any disorder in which liver production of a specific protein is therapeutic.

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“…These previous treatments may also have positively contributed to the present results via their immunomodulatory effects. According to recent reports, mogamulizumab has been shown to decrease the level of CCR4 + regulatory T cells (Ishida & Ueda, 2011), and lenalidomide has immunomodulatory effects indirectly enhancing the activity of natural killer and T cells (Wu et al, 2008;De Keersmaecker et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Clinical outcomes of a novel therapeutic vaccine with Tax peptide‐pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study

et al. 2015

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Summary Adult T cell leukaemia/lymphoma (ATL) is a human T cell leukaemia virus type‐I (HTLV‐I)‐infected T cell malignancy with poor prognosis. We herein developed a novel therapeutic vaccine designed to augment an HTLV‐I Tax‐specific cytotoxic T lymphocyte (CTL) response that has been implicated in anti‐ATL effects, and conducted a pilot study to investigate its safety and efficacy. Three previously treated ATL patients, classified as intermediate‐ to high‐risk, were subcutaneously administered with the vaccine, consisting of autologous dendritic cells (DCs) pulsed with Tax peptides corresponding to the CTL epitopes. In all patients, the performance status improved after vaccination without severe adverse events, and Tax‐specific CTL responses were observed with peaks at 16–20 weeks. Two patients achieved partial remission in the first 8 weeks, one of whom later achieved complete remission, maintaining their remission status without any additional chemotherapy 24 and 19 months after vaccination, respectively. The third patient, whose tumour cells lacked the ability to express Tax at biopsy, obtained stable disease in the first 8 weeks and later developed slowly progressive disease although additional therapy was not required for 14 months. The clinical outcomes of this pilot study indicate that the Tax peptide‐pulsed DC vaccine is a safe and promising immunotherapy for ATL.

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Expansion of Polyfunctional HIV-Specific T Cells upon Stimulation with mRNA Electroporated Dendritic Cells in the Presence of Immunomodulatory Drugs

Cited by 15 publications

References 52 publications

Treatment with lenalidomide induces immunoactivating and counter-regulatory immunosuppressive changes in myeloma patients

Treatment with lenalidomide induces immunoactivating and counter-regulatory immunosuppressive changes in myeloma patients

Development of gene therapy for blood disorders: an update

Clinical outcomes of a novel therapeutic vaccine with Tax peptide‐pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study

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