Photodepletion to Promote Immune Reconstitution Without Graft-Versus-Host Disease After HLA-Haploidentical Transplantation

Chapter
Part of the Advances and Controversies in Hematopoietic Transplantation and Cell Therapy book series (ACHTCT)

Abstract

Haploidentical hematopoietic cell transplantation (haplo-HCT) offers an immense challenge in terms of immunologic difference between donor and recipient cells. However, this major histocompatibility complex (MHC) disparity also represents a powerful tool for the ex vivo removal of alloreactive cells. Indeed, we found that it promotes donor T-cell activation upon exposure to host T-cells and leads to their selective elimination after exposure to a rhodamine-derived photosensitizer (TH9402) and visible light. In this chapter, we highlight the road to development of selectively depleted good manufacturing practice (GMP)-grade T-lymphocyte products (ATIR™, Kiadis Pharma, NL), from mechanistic determinants to bedside. This strategy enables haplo-HCT without the use of immune suppressors. A phase I clinical trial was able to identify a therapeutic ATIR cell dose associated with a decrease in infectious complications and treatment-related mortality (TRM). Long-term follow-up of these patients shows sustained remission in high-risk patients, suggesting preservation of graft-versus-leukemia activity in ATIR cells. Results from an ongoing phase II clinical trial in 23 acute leukemia patients using a single dose of ATIR at 2 million CD3+ cells/kg are in line with phase I outcomes. ATIR infusion also harbors the potential to promote immune reconstitution in different types of haplo-HCT.

Keywords

Photodepletion Immune reconstitution Graft-versus-host disease Haploidentical transplantation Rhodamine-derived photosensitizer Photopheresis 

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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.CellCAN: Canadian Regenerative Medicine and Cell Therapy NetworkUniversite de MontrealMontrealCanada
  2. 2.TheCell-FRQS: Quebec Cell, Tissue and Gene Therapy NetworkQuebecCanada
  3. 3.Centre of Excellence for Cell TherapyHopital Maisonneuve-RosemontMontrealCanada
  4. 4.Karolinska Institute and University HospitalStockholmSweden

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