CMV Specific T Cell Therapy After Allogeneic Stem Cell Transplantation.
Condition: Hematological Malignancies; CMV Infection
MeSH terms: Infections; Cytomegalovirus Infections; Hematologic Neoplasms
Study type: Interventional
Phase: Phase 2

Summary: 
      Viral infections remain an important cause of morbidity and mortality after allogeneic stem
      cell transplantation (SCT), especially after myelo-ablative conditioning and if the donor is
      antigen-mismatched or haplo-identical.. In the described setting the patient's own immune
      system has been destroyed by the necessary highly immuno- and myelo-ablative conditioning and
      all memory against infections has been deleted. Therefore, there is a high risk for several
      viral infections and other infectious organisms.Both primary viral infections and
      reactivations can occur, and patients can become refractory to antiviral treatments, or in
      some cases an adequate antiviral treatment is unavailable or too toxic. In this study, the
      investigators will target CMV, as refractory CMV infection and disease is accompanied by an
      extremely high mortality rate and therefore the development of new treatment approaches is
      required. Despite the available antiviral drugs, a considerable number of patients are facing
      an insufficient control of CMV reactivation after SCT. Because reconstitution of CMV-specific
      T cells confer protection against the development of CMV disease after SCT, attempts have
      been made to restore antiviral immunity by direct infusion of CMV-specific T cells. Most
      clinical cellular immunotherapy protocols for CMV treatment have used CMV-specific cytotoxic
      CD8+ T-cell lines generated by repetitive in vitro stimulation with CMV antigens with
      success. Despite the proven efficacy, use of cellular therapy in the clinic has been limited,
      because the approach is time and labor consuming and requires specialized facility allowing
      handling of the therapeutic cells according to good manufacturing practice. In addition, no
      sustained response was seen after adoptive transfer that involved only cytotoxic CD8+ T
      cells. This phenomenon is supported by the fact that recall responses to latent infections
      depend on the presence of CD4+ T cells to help cytotoxic CD8+ T cells. An alternative
      approach for the transfer of T-cell immunity is the isolation of Ag-specific T cells ex vivo
      from the blood of CMV seropositive donors, based on interferon γ (IFN-γ) secretion of T cells
      after in vitro stimulation with viral Ag, resulting in a combination of CD4+ T helper and
      cytotoxic CD8+ CMV specific T cells. Using this strategy, a short-term ex vivo protocol was
      developed for the isolation of pp65 (CMV immunodominant protein)-specific T cells. Since
      then, several centers have used this protocol in the clinic, infusing low numbers of
      pp65-specific T cells, that were able to restore protective T-cell immunity against CMV in a
      post SCT setting in patients with refractory CMV disease or viremia. For this protocol the
      investigators have set up and validated this method of CMV-specific T-cell generation in the
      Ghent University Hospital and the investigators will make it available for other Belgian
      transplant centers.
    


Intervention name(s): CMV-specific T cells; Standard anti-viral therapy
Intervention type(s): Genetic; Drug
Intervention description(s): Continue with the anti-viral treatment as per standard of care.
Intervention MeSH terms: Antiviral Agents
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: allogeneic stem cell transplantation; CMV reactivation