Clearance of Treatment Refractory Adenoviremia via Adenovirus-specific Donor T-Cell Transfer During Aplasia After αβTCR-CD19–Depleted Stem Cell Transplantation

2018 ◽  
Vol 68 (8) ◽  
pp. 1406-1409 ◽  
Author(s):  
Katharina L Gössling ◽  
Hiba Fouz ◽  
Olga Kyrillopoulou ◽  
Matthias Aubin ◽  
Britta Maecker-Kolhoff ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Transfer ◽  
Treatment Refractory ◽  
T Cell Transfer

Simultaneous Isolation and Enrichment of Multi Specific and Multi Functional T-Cells Populations for Treatment of Patients Undergoing Allogeneic Hematopoetic Stem Cell Transplantation,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4056-4056
Author(s):  
Meike Kruse ◽  
Halvard Bonig ◽  
Markus Kapp ◽  
Lothar Germeroth ◽  
Hermann Einsele ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Transfer ◽  
Hematopoetic Stem Cell ◽  
Healthy Donors ◽  
T Cell Transfer ◽  
Hematopoetic Stem Cell Transplantation

Abstract Abstract 4056 Allogeneic hematopoetic stem cell transplantation (aHSCT) is a treatment option for a variety of diseases in particular heamatological malignancies. Due to an ongoing immunosuppression to prevent graft versus host reaction (GvHD), disease relapses as well as viral infections are major causes of morbidity and mortality after aHSCT. T cell responses against different tumor-associated and tumor-specific antigens could be detected not only in patients with malignant diseases but also in healthy donors. We investigated the selection of MART-1 (Melanoma Antigen Recognized by T-cells), Proteinase 3 and WT-1 (Wilms Tumor- Antigen) specific T cells from the blood of healthy donors as basis for a tumor-specific T cell transfer in the context of aHSCT. With a newly established protocol, based on streptamer selection, we isolated simultaneously multi-functional and multi-specific T-cell populations. We selected tumor-antigen-specific CTL′s (Cytotoxic T- Lymphocytes) mentioned above and also antiviral T-cells namely against CMV, EBV and AdV from a single blood donation. In this simultaneous selection with up to 7 different epitopes in one step, even the tumor specific T cells, which are known to be rarely detected among healthy donors, could be enriched to an amount sufficient for a direct T cell transfer. Purity achieved after selection was at least 82% and up to 98,87%, which minimizes the risk for GvHD after clinical application. The possibility to transfer these selected CTL`s to patients after stem cell transplantation improves the graft versus tumor effect as well as the anti infective T cell immunity without a relevant risk for GvHD. Furthermore, the selected multi specific T cell populations could be expanded in vitro without loss of specificity and include different phenotypes such as central memory and memory effector cells, which may provide long lasting immunity. Moreover, starting with a leukapheresis, we successfully transferred our selection protocol in a closed system according to current good manufacturing practice (cGMP) requirements, which allows clinical application in the future. With that, it opens new perspectives in cellular immunotherapy against malignancies and viral infection for patients after aHSCT. Disclosures: No relevant conflicts of interest to declare.

Adoptive Transfer of Adenovirus Specific T-Cells in Children with Systemic Adenovirus Infection after Allogeneic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 80-80
Author(s):  
Tobias F. Feuchtinger ◽  
Susanne Matthes-Martin ◽  
Celine Richard ◽  
Thomas Lion ◽  
Klaus Hamprecht ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Adoptive Transfer ◽  
Cell Transfer ◽  
New Treatment ◽  
T Cell Transfer

Abstract Allogeneic stem cell transplantation (SCT) has become an increasing treatment option for a variety of malignant and non-malignant disease. During immune reconstitution the host is at significant risk for viral infections. Human adenovirus (HAdV) infection is especially in children an important and serious complication. Virus-specific T-cells are essential for the clearance of HAdV, since antiviral chemotherapy has been insufficient to date. We present a new treatment option using virus-specific donor T-cells for adoptive transfer of immunity to patients with systemic HAdV-infection. We isolated in 6 patients with systemic HAdV-infection after SCT virus-specific T-cells of the donor, according to INF-γ secretion after short in vitro stimulation with viral antigen, resulting in a combination of CD4+ and CD8+ T-cells. Between 5-50x103/kg T-cells were infused for adoptive transfer. For follow-up, the infection and the in-vivo expansion of infused T-cells were evaluated. Isolated cells showed high specificity and markedly reduced but residual alloreactivity in-vitro. In three of four evaluable patients the infused T-cells underwent an in-vivo expansion and in these three patients the viral load decreased in peripheral blood after adoptive T-cell transfer. In-vivo expansion of specific T-cells was dose-independent. T-cell infusion was well tolerated. One patient experienced GvHD°II of the skin after T-cell transfer. In conclusion specific T-cell immunotherapy as a new treatment approach for children was performed in 6 cases of systemic HAdV-infection after allogeneic SCT. Induction of a specific T-cell response through adoptive transfer has been shown feasible and effective to protect from HAdV-related complications.

Streptamer Technology for the Assessment of CMVpp65 Specific CD8+ T Cell Frequencies and for the Adoptive T Cell Transfer to Post-Transplant Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1964-1964
Author(s):  
Anita Schmitt ◽  
Junxia Yao ◽  
Hermann Einsele ◽  
Ulrich Grigoleit ◽  
Dirk Busch ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cd8 T Cells ◽  
Cd8 T Cell ◽  
Cell Transfer ◽  
Adoptive T Cell Transfer ◽  
T Cell Transfer ◽  
Cmv Antigenemia

Abstract Cytomegalovirus (CMV) reactivation constitutes a serious complication after allogeneic peripheral blood stem cell transplantation (PBSCT). The frequency of CMVpp65 specific CD8+ T cells is pivotal for the clearance of CMV. CMVpp65 specific CD8+ T cell frequencies can be measured using tetra-, penta- and streptamer technologies, streptamers can also be applied therapeutically. In donors, these frequencies might allow us to define the best available donor in addition to the mere serostatus. In the present study we investigated the specificity and sensitivity of all three methods and compared the results to the serostatus. A therapeutical application, i.e. an adoptive transfer of CMV specific CD8+ T cells selected by streptamer technology to a patient with acute lymphatic leukemia suffering from life-threatening CMV antigenemia after allogeneic PBSCT was performed. 23 samples from CMV seropositive healthy volunteers (HV) and 10 samples from CMV seropositive patients before and after allogeneic stem cell transplantation (all HLA-A2 or -B7 positive) were analyzed with tetra-, penta- or streptamer conjugated to PE by flow cytometry. Our lab took part in an inter-lab CMV multimer assay including 20 European countries in the framework of www.kimt.de. For the adoptive T cell transfer a donor leukapheresis was performed followed by an HLA-B7 CMVpp65 streptamer positive selection. The patient received 2×10E5 CMV specific CD8+ T cells per kg body weight as a single transfusion. Optimal amounts of HLA-A2 multimers to stain a pellet of 10E6 cells were 0.44 mcg tetramer, 0.15 mcg pentamer and 0.2 mcg MHC/0.3 mcg streptactin complex. Surprisingly, only in 48% (11/23) seropositive HV CD8+ multimer+ T cells could be detected. The ALL patient developed a foscarvir resistant CMV antigenemia with a maximum of 959/500,000 CMVpp65 positive cells. After a switch to ganciclovir/valganciclovir and an adoptive transfer of CMV specific T cells, the antigenemia was cleared. Valganciclovir was discontinued, but CMV antigenemia remained controlled. The frequency of CMVpp65 specific CD8+ T cells increased dramatically from 0.0% till 19.8%. All of these T cells were donor derived as demonstrated by small tandem repeat (STR) analysis. The patient did not develop signs of CMV disease at any time point. This study demonstrates the power of multimer staining to define appropriate donors for transplantation. Donors should be screened for their CMVpp65 specific CD8+ T cell frequency. All three multimer technologies can be used yielding similar results. The streptamer technology additionally offers the advantage to select CMVpp65 specific CD8+ T cells at the GMP level for adoptive T cell transfer and can induce long-lasting CD8+ T cell responses effectively clearing even a high virus load.

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