Graft Versus Leukemia Response Without Graft-versus-host Disease Elicited By Adoptively Transferred Multivirus-specific T-cells

Melenhorst, J. Joseph; Castillo, Paul; Hanley, Patrick J.; Keller, Michael D.; Krance, Robert A.; Margolin, Judith F.; Leen, Ann M.; Heslop, Helen E.; Barrett, A. John; Rooney, Cliona M.; Bollard, Catherine M.

doi:10.1038/mt.2014.192

Cited by 25 publications

(19 citation statements)

References 35 publications

(37 reference statements)

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“…Only four responders had recurrence or progression. GvHD developed in eight patients (two of them showed de novo GvHD, and in only one of grade 3) confirming previous observations [107,108]. Most interestingly, the VSTCs used in this study were "off-the-shelf" and only partially HLA-matched.…”

Section: Recent Developments: Third-party Vstcs and Naïve Donors T-cesupporting

confidence: 69%

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

Madon

Giaccone

Festuccia

et al. 2016

Expert Review of Hematology

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Section: Recent Developments: Third-party Vstcs and Naïve Donors T-cesupporting

confidence: 69%

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

Madon

Giaccone

Festuccia

et al. 2016

Expert Review of Hematology

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“…Functionality of the T-cells was assessed by the flow cytometric detection of intracellular accumulation of IFN-γ, granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α), and CD40 ligand (CD40L) (all from BD Biosciences) as previously described. (48, 49) Briefly, T-cells were stimulated with 1 μg/mL final concentration of each Pepmix; medium alone was used as the negative control. After incubation for 1 hour at 37°C, 10 μg/mL of Brefeldin A (Sigma) was added for an addition 5 hours.…”

Section: Methodsmentioning

confidence: 99%

CMV-specific T cells generated from naïve T cells recognize atypical epitopes and may be protective in vivo

et al. 2015

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Adoptive transfer of adult-seropositive, cytomegalovirus (CMV)-specific T-cells can effectively restore antiviral immunity after transplantation. Lack of CMV-specific memory T-cells in blood from CMV-seronegative adult and cord blood (CB) donors restricts the availability of donor-derived virus-specific T-cells for immunoprophylaxis. Here we demonstrate the feasibility of naïve-donor-derived CMV-specific T-cell therapy for transplant recipients. Primed naïve T-cells recognized only atypical epitopes and with a similar avidity to CMV-seropositive-derived T-cells recognizing typical epitopes, but T-cells from CMV-seropositive donors recognizing atypical epitopes had a lower avidity suggesting the loss of high-avidity T-cells over time. Clonotypic analysis revealed T-cells recognizing atypical CMVpp65 epitopes in the peripheral blood of recipients of CB grafts who did not develop CMV. T-cell receptors from atypical epitopes were most common in unmanipulated CB units explaining why these T-cells expanded. When infused to recipients, naïve donor-derived virus specific T-cells that recognized atypical epitopes were associated with prolonged periods of CMV-free survival and complete remission.

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“…Antigen-specific T cells such as virus-specific cytotoxic T lymphocytes can expand in vivo, actively traffic to tumor sites, expand upon exposure to antigens, and persist long term. Moreover, activated T cells can recruit additional and distinct sets of cellular and cytokine-mediated effector mechanisms once antigen is recognized [5–8]. Given the desirable properties of these cell therapies, there has been great interest in adoptively transferring T cells capable of recognizing and destroying human tumors.…”

Section: Introductionmentioning

confidence: 99%

Improving the safety of T-Cell therapies using an inducible caspase-9 gene

Zhou

Brenner

2016

Experimental Hematology

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Adoptive transfer of T cells can be an effective anti-cancer treatment. However, uncontrolled or unpredictable immediate or persistent toxicities are a source of concern. The ability to conditionally eliminate aberrant cells in vivo therefore is becoming a critical step for the successful translation of this approach to the clinic. We review the evolution of safety systems, focusing on a suicide switch that can be expressed stably and efficiently in human T cells without impairing phenotype, function or antigen specificity. This system is based on the fusion of human caspase 9 to a modified human FK-binding protein, allowing conditional dimerization in the presence of an otherwise bioinert small molecule drug. When exposed to the synthetic dimerizing drug, the inducible caspase 9 (iC9) becomes activated and leads to the rapid apoptosis of cells expressing this construct. We have demonstrated the clinical feasibility and efficacy of this approach after haploidentical hematopoietic stem cell transplant (haplo-HSCT). Here we review the benefits and limitations of the approach.

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Graft Versus Leukemia Response Without Graft-versus-host Disease Elicited By Adoptively Transferred Multivirus-specific T-cells

Cited by 25 publications

References 35 publications

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

Treatment of CMV infection after allogeneic hematopoietic stem cell transplantation

CMV-specific T cells generated from naïve T cells recognize atypical epitopes and may be protective in vivo

Improving the safety of T-Cell therapies using an inducible caspase-9 gene

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