Pro5® Pentamers central in life-saving procedure for PTLD treatment

Uhlin, M. et al. (2009). A novel haplo-identical adoptive CTL therapy as a treatment for EBV-associated lymphoma after stem cell transplantation. Cancer Immunol Immunother. 59(3): 473-477. [PubMed ID: 19908041]

Michael Uhlin Michael Uhlin (photo left) and colleagues described the first use of Pro5® Pentamers in a rapid method for isolating EBV specific T cells for adoptive cytotoxic T lymphocytes (CTL) transfer. 

Three months after receiving a cord blood transplant for acute myeloid leukemia, the patient presented with Epstein-Barr virus (EBV) associated lymphoma, high blood EBV titers and lesions in the lungs, liver, adrenal gland and kidneys indicative of post-transplant lymphoproliferative disorder (PTLD). The patient was unresponsive to standard PTLD treatments and as no other options were available, adoptive EBV-specific CTL transfer from the patient’s mother was considered.

Given the life-threatening situation for the patient, a rapid method for CTL preparation was required. EBV specific T cells (A*0201/GLCTLVAML) from the maternal blood were stained using Pro5® Pentamers and subsequently labeled with magnetic beads allowing a quick and simple isolation of the Pentamer positive cells. The antigen-specific cells were injected intravenously into the patient at a concentration of 1.1×104CTL/kg.

Figure 1: Representative experimental data showing EBV-specific cells (A*0201/GLCTLVAML or A*0201/CLGGLLTMV) stained with Pro5® MHC Pentamer. These can then be labeled with magnetic beads and separated out for transfer to the recipient.

After only 36 hours, the frequency of Pentamer-positive antigen-specific T cells detected in the patient increased from 0.3% of total CD8+ cells to 4.4%, indicating that the donor cells had expanded rapidly in vivo. Furthermore, following the CTL transfusion, EBV titers decreased back to normal levels almost immediately. Prior to CTL infusion a CT scan showed considerable growth of lymphoma in the lungs, liver, adrenal gland and kidney. 189 days later, a comparative CT scan showed only remnant streaks in the thorax, no sign of lesions in the liver and only minor lesions in the kidney. Additionally the left adrenal gland returned to normal size. At 12 months post-transplant, after being admitted with EBV virus in the tonsils, blood and colon, the patient was given a second infusion, using Pro5® Pentamers to isolate both A*0201/GLCTLVAML and additional A*0201/CLGGLLTMV EBV specific cells (2×104 CTL/kg). By 72 hours post-infusion, all signs of tonsillitis and enteritis had been cured.

The use of the Pro5® Pentamers was central to developing this novel and successful method for treatment of EBV-associated complications following stem cell transplantation and offers new life-saving strategies for rapid treatment of PTLD patients.

2011: Three years after treatment, the patient continues to thrive, and Michael Uhlin and his co-workers continue to explore the potential offered by adoptive T-cell therapy.  Read editorial in Immunotherapy. [PubMed ID: 21322751]