scholarly journals Cytomegalovirus (CMV)-Specific Polyfunctional T-Cell Responses after Letermovir (LET) Prophylaxis in Hematopoietic Cell Transplantation (HCT)

2020 ◽  
Vol 26 (3) ◽  
pp. S68-S69 ◽  
Author(s):  
Danniel Zamora ◽  
Brenda Akoto ◽  
Hu Xie ◽  
Richard Kiener ◽  
Bradley C. Edmison ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
T Cell Responses ◽  
Hematopoietic Cell ◽  
Cell Responses

scholarly journals Cytomegalovirus-specific T-cell Reconstitution following Letermovir Prophylaxis after Hematopoietic Cell Transplantation

Blood ◽  
2021 ◽  
Author(s):  
Danniel Zamora ◽  
Elizabeth R Duke ◽  
Hu Xie ◽  
Bradley C Edmison ◽  
Brenda B. Akoto ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
T Cell Responses ◽  
Hematopoietic Cell ◽  
T Cell Subsets ◽  
Preemptive Therapy ◽  
Color Flow ◽  
Cell Responses ◽  
Cell Immunity

Decreased cytomegalovirus (CMV)-specific immunity after hematopoietic cell transplantation (HCT) is associated with late CMV reactivation and increased mortality. Whether letermovir prophylaxis-associated reduction in viral exposure influences CMV-specific immune reconstitution is unknown. We compared polyfunctional CMV-specific T-cell responses in a prospective cohort of allogeneic HCT recipients who received letermovir to controls who received PCR-guided preemptive therapy prior to the introduction of letermovir. Thirteen-color flow cytometry was used to assess T-cell responses at three months post-HCT following stimulation with CMV immediate early-1 (IE-1) antigen and phosphoprotein 65 (pp65) antigens. Polyfunctionality was characterized by combinatorial polyfunctionality analysis of antigen specific T-cell subsets (COMPASS). Letermovir use and reduction in viral exposure were assessed for their association with CMV-specific T-cell immunity. Polyfunctional T-cell responses to IE-1 and pp65 were decreased in letermovir recipients and remained diminished after adjusting for donor CMV serostatus, absolute lymphocyte count, and steroid use. Among letermovir recipients, greater peak CMV DNAemia and increased viral shedding were associated with stronger CD8+ responses to pp65; whereas CMV shedding rate was associated with greater CD4+ responses to IE-1. In conclusion, our study provides initial evidence that letermovir may delay CMV-specific cellular reconstitution, possibly due to decreased CMV antigen exposure. Evaluating T-cell polyfunctionality may identify patients at risk for late CMV infection after HCT.

scholarly journals Analysis of transgene-specific immune responses that limit the in vivo persistence of adoptively transferred HSV-TK–modified donor T cells after allogeneic hematopoietic cell transplantation

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2294-2302 ◽  
Author(s):  
Carolina Berger ◽  
Mary E. Flowers ◽  
Edus H. Warren ◽  
Stanley R. Riddell
Keyword(s):  
T Cells ◽  
T Cell ◽  
Immune Responses ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
T Cell Responses ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Cell Responses ◽  
Donor T Cells

AbstractThe introduction of an inducible suicide gene such as the herpes simplex virus thymidine kinase (HSV-TK) might allow exploitation of the antitumor activity of donor T cells after allogeneic hematopoietic cell transplantation (HCT) without graft versus host disease. However, HSV-TK is foreign, and immune responses to gene-modified T cells could lead to their premature elimination. We show that after the infusion of HSV-TK–modified donor T cells to HCT recipients, CD8+ and CD4+ T-cell responses to HSV-TK are rapidly induced and coincide with the disappearance of transferred cells. Cytokine flow cytometry using an overlapping panel of HSV-TK peptides allowed rapid detection and quantitation of HSV-TK–specific T cells in the blood and identified multiple immunogenic epitopes. Repeated infusion of modified T cells boosted the induced HSV-TK–specific T cells, which persisted as memory cells. These studies demonstrate the need for nonimmunogenic suicide genes and identify a strategy for detection of CD4+ and CD8+ T-cell responses to transgene products that should be generally applicable to monitoring patients on gene therapy trials. The potency of gene-modified T cells to elicit robust and durable immune responses imply this approach might be used for vaccination to elicit T-cell responses to viral or tumor antigens.

scholarly journals HLA-DP in unrelated hematopoietic cell transplantation revisited: challenges and opportunities

Blood ◽  
2017 ◽  
Vol 130 (9) ◽  
pp. 1089-1096 ◽  
Author(s):  
Katharina Fleischhauer ◽  
Bronwen E. Shaw
Keyword(s):  
T Cell ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Cellular Immunotherapy ◽  
Blood Disorders ◽  
Cell Responses ◽  
Challenges And Opportunities ◽  
Unrelated Donors ◽  
Alloreactive T Cell

Abstract When considering HLA-matched hematopoietic cell transplantation (HCT), sibling and unrelated donors (UDs) are biologically different because UD-HCT is typically performed across HLA-DP disparities absent in sibling HCT. Mismatched HLA-DP is targeted by direct alloreactive T cell responses with important implications for graft-versus-host disease and graft-versus-leukemia. This concise review details special features of HLA-DP as model antigens for clinically permissive mismatches mediating limited T-cell alloreactivity with minimal toxicity, and describes future avenues for their exploitation in cellular immunotherapy of malignant blood disorders.

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