Abstract

During the last decade, many studies have demonstrated the role of CMV specific T-cell immune response on controlling CMV replication and dissemination. In fact, it is well established that transplanted patients lacking CMV-specific T-cell immunity have an increased occurrence of CMV replication episodes and CMV-related complications. In this context, the use of adoptive transfer of CMV-specific T-cells has been widely investigated and applied to Hematopoietic Stem Cell Transplant patients and may be useful as a therapeutic alternative, to reconstitute the CMV specific T-cell response and to control CMV viremia in patients receiving a transplantation. However, only few authors have explored the use of T-cell adoptive transfer in SOT recipients. We propose a novel review in which we provide an overview of the impact of using CMV-specific T-cell adoptive transfer on the control of CMV infection in SOT recipients, the different approaches to stimulate, isolate and expand CMV-specific T-cells developed over the years and a discussion of the possible use of CMV adoptive cellular therapy in this SOT population. Given the timeliness and importance of this topic, we believe that such an analysis will provide important insights into CMV infection and its treatment/prevention.

Highlights

  • Viral infection, including cytomegalovirus (CMV), BK virus and Epstein-Barr virus, remains a major cause of morbidity and mortality in immunocompromised individuals [1,2,3,4,5]

  • CMV seropositive allogeneic Hematopoietic Stem Cell Transplant (HSCT) patients presents the highest risk of recurrent infections, followed by CMV seronegative solid organ transplantation (SOT) recipients that receive a graft from a seropositive donor (R-/D+), HIV patients, and patients who have received T-cell depletion therapies [6, 7]

  • Together these results suggest that, there is still space for improvement, the use of CMV-specific T-cell adoptive transfer is promising in SOT recipients with limited options for CMV-infection treatment

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Summary

INTRODUCTION

Viral infection, including cytomegalovirus (CMV), BK virus and Epstein-Barr virus, remains a major cause of morbidity and mortality in immunocompromised individuals [1,2,3,4,5]. Evidences of immunological reconstitution was associated with control of viremia [48] Based on these promising results, several clinical studies are currently been conducted: (i) A clinical trial (NCT03665675) including 20 patients, both HSCT recipients and SOT recipients is been conducted, to study the effect of transferring allogeneic CMV-specific T lymphocytes on CMV infection or reactivation. (iv) A clinical trial (NCT03266640) with 20 participants investigating the therapeutic role of CMV CTLs in children, adolescents and young adults (CAYA) with refractory CMV infection post allogeneic HSCT or SOT Together these results suggest that, there is still space for improvement, the use of CMV-specific T-cell adoptive transfer is promising in SOT recipients with limited options for CMV-infection treatment

CELLULAR THERAPIES AVAILABLE
Stimulation method
Fresh expansion
Cytoquine capture Activation marker
Cell Therapy Limitations and Alternatives in SOT Patients
FUTURE DIRECTIONS AND PERSPECTIVES
CONCLUSIONS
Findings
AUTHOR CONTRIBUTIONS
Full Text
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