scholarly journals Transfer of Hexon‐ and Penton‐selected adenovirus‐specific T cells for refractory adenovirus infection after haploidentical stem cell transplantation

2019 ◽  
Vol 22 (1) ◽  
Author(s):  
Rebecca E. Schultze‐Florey ◽  
Sabine Tischer‐Zimmermann ◽  
Hans‐Gert Heuft ◽  
Christoph Priesner ◽  
Britta Lamottke ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Adenovirus Infection ◽  
Haploidentical Stem Cell Transplantation

scholarly journals Combined CD8+ and CD4+ adenovirus hexon-specific T cells associated with viral clearance after stem cell transplantation as treatment for adenovirus infection

Haematologica ◽  
2010 ◽  
Vol 95 (11) ◽  
pp. 1943-1951 ◽  
Author(s):  
M. L. Zandvliet ◽  
J. H. F. Falkenburg ◽  
E. van Liempt ◽  
L. A. Veltrop-Duits ◽  
A. C. Lankester ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Viral Clearance ◽  
Adenovirus Infection

Immune Reconstitution and Immune Correlates of Clinical Outcome IN Acute LEUKEMIA PATIENTS Treated with Haploidentical STEM CELL TRANSPLANTATION.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 46-46
Author(s):  
Alessandra Forcina ◽  
Maddalena Noviello ◽  
Veronica Valtolina ◽  
Attilio Bondanza ◽  
Daniela Clerici ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Immune Reconstitution ◽  
Patient Specific ◽  
Haploidentical Stem Cell Transplantation ◽  
Gvhd Prophylaxis ◽  
Kinetics Of

Abstract Abstract 46 The broader application of haploidentical stem cell transplantation (haplo-HCT), is limited by the delayed immune reconstitution (IR) secondary to the procedures for GvHD prophylaxis. This ultimately results in a high-rate of infectious complications and non-relapse mortality. We dynamically analyzed immunoreconstitution (IR) in patients undergoing haplo-HCT for acute leukemias enrolled in two different phase I-II clinical trials aimed at improving IR. In the first trial (TK007), 28 patients (out of 50 enrolled) received suicide-gene transduced donor T cells at day +42 after a T-cell depleted graft, in the absence of post-transplant immunosuppression. In the second trial (TrRaMM), 40 patients received an unmanipulated graft and a rapamycin-based GvHD prophylaxis. T-cell immune reconstitution was more rapid in TrRaMM than in TK007 patients, with a threshold of CD3 cells>100/μl reached at days +30 and +90, respectively. In both trials IR was mainly composed of Th1/Tc1 lymphocytes with an inverted CD4/CD8 ratio. While in TrRaMM patients we observed an early expansion of naïve and central memory T cells, producing high amounts of IL-2, in TK patients IR was mainly composed of activated effectors. Furthermore, in TrRaMM patients we detected high levels of CD4+CD25+CD127- T regulatory cells (up to 15% of circulating T lymphocytes) that persisted after rapamycin withdrawal, and was significantly superior to that observed in TK patients and in healthy controls. Interestingly, in contrast to the different kinetics of T-cell reconstitution, no differences were observed in time required to gain protective levels of CMV-specific T cells, as shown by ψIFN ELISPOT analysis. Protective frequencies of CMV-specific lymphocytes were observed 3 months after HCT in both groups, a time-point that in TrRaMM patients corresponds to the average time of rapamycin withdrawal. In both trials the number of circulating CMV-specific T cells was inversely correlated to the number and severity of subsequent CMV reactivations and days of antiviral therapy. GvHD was diagnosed in 16 TrRaMM patients (40%) and in 10 TK patients (35% of patients who received TK cells). Severity of GvHD was different in the two cohort of patients with 5 TrRaMM patients (12,5%) and only 2 TK patients (7%) with grade III-IV GvHD. Of interest, in the TrRaMM group CMV-specific immunity was significantly hampered by the immunosuppressive treatment required to treat GvHD. On the contrary, in the TK group, the administration of ganciclovir was able to activate the suicide machinery and control GvHD without impairing viral-specific T-cell immunocompetence. These results matched with the kinetics of CMV reactivations. We observed that while in TrRaMM patients 80% of viral reactivations occurred after the immunosuppressive therapy, in TK patients no significant differences could be assessed before and after therapy. IFN-ψ ELISPOT might thus be a relevant and predictive test to guide patient-specific clinical monitoring and antiviral treatment. Overall, these results show that early immune reconstitution can be promoted in haplo-HCT by different strategies associated with a wide range of alloreactive potential. The risks and benefits associated with alloreactivity should guide the therapeutic choice tuned on patient disease status and co-morbidities. Disclosures: Bordignon: Molmed Spa: Employment.

scholarly journals C-10. Inducible Caspase-9 Suicide Gene Controls Adverse Effects from Alloreplete T Cells after Haploidentical Stem Cell Transplantation

2015 ◽  
Vol 23 ◽  
pp. S103
Author(s):  
Xiaoou Zhou ◽  
Gianpietro Dotti ◽  
Robert A. Krance ◽  
Caridad Martinez ◽  
Rammurti T. Kamble ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Adverse Effects ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Suicide Gene ◽  
Caspase 9 ◽  
Haploidentical Stem Cell Transplantation

Adoptive Immunotherapy after Haploidentical Stem Cell Transplantation with T Cells Allodepleted by Photodynamic Purging

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1157-1157
Author(s):  
Katia Perruccio ◽  
Fabiana Topini ◽  
Antonella Tosti ◽  
Alessandra Carotti ◽  
Teresa Aloisi ◽  
...  
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Adoptive Immunotherapy ◽  
Cell Responses ◽  
Alloreactive T Cells ◽  
Haploidentical Stem Cell Transplantation ◽  
Donor T Cells

Abstract After haploidentical stem cell transplantation, immune recovery is slow due to decaying thymic function and extensive T-cell depletion of the graft which is needed to prevent Graft-versus-Host Disease (GvHD). Consequently, infectious related mortality is about 30–40%. To address this problem, we investigated the efficacy of adoptive immunotherapy after photodynamic purging of alloreactive T cells (ATIR, Kiadis Pharma, Amsterdam, The Netherlands) in preventing GvHD and improving immune reconstitution. The 4,5-dibromorhodamine methyl ester (TH9402) is a photosensitizer structurally similar to rhodamine. When donor T cells are activated with allogeneic cells, they retain TH9402 which becomes highly cytotoxic upon activation with visible light. MLR-activated donor T cells are exposed to a fluorescent-light scanning device to eliminate alloreactive T cells. We designed a protocol which provided 3,260 ± 450 (mean ± SD)-fold allodepletion, full retention of T-regulatory cells, and preservation of pathogen- and leukaemia-specific T-cell responses (against Aspergillus, Candida, Cytomegalovirus (CMV), Adenovirus (ADV), Herpes Simplex Virus (HSV), Varicella Zoster Virus (VZV), Toxoplasma antigens; and against leukaemia cells and leukaemia antigens (WT1 and Ca125)). Optimized protocol conditions are: MLR cell concentration: 3–5 × 10e6/ml; MLR duration: 24 hours; TH9402 concentration: 5 μM; TH9402 incorporation, as measured by median fluorescence index (MFI): 20,000 – 25,000; energy delivery: 0.1 J/cm2. Here we present the preliminary results of a clinical trial. Escalating doses of photodynamically allodeleted donor T cells, i.e., 1.25 × 10e5/Kg, 2.5 × 10e5/Kg, 5 × 10e5/Kg, 1 × 10e6/Kg and 1.25 × 10e6/Kg, were infused into groups of haploidentical transplant recipients. Only 1 patient developed grade III aGvHD at the 1 × 10e6/Kg cell dose and responded to immune suppressive treatment. Immune assessment analyses revealed that infusion of cell doses equal or greater than 5 × 10e5/Kg are associated with significant reconstitution of T-cell counts and appearance of pathogen-specific T-cell responses. One month after infusion, CD4+ and CD8+ T cells were 124 ± 54/cmm and 327 ± 42/cmm (versus 11 ± 4/cmm and 8 ± 4/cmm respectively, in patients receiving T-cell doses below 5 × 10e5/Kg, P = 0.0007). Aspergillus, Candida, CMV, ADV, HSV, VZV, Toxoplasma-specific CD4+ and CD8+ T-cell responses had recovered to frequencies within the normal ranges while they were absent in patients who received T cell doses under 5 × 10e5/Kg (P = 0.0002). In conclusion, this study demonstrates the feasibility, safety and preliminary indications of efficacy of adoptive immunotherapy after photodynamic purging of alloreactive T cells in recipients of haploidentical stem cell transplantation. A larger study will evaluate the impact of these T-cell infusions on transplant related mortality and disease free survival.

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