308 Viral-Specific T Lymphocytes for Treatment of Viral Infections in Primary Immunodeficiency

Track: Poster Abstracts
Wednesday, February 11, 2015, 6:45 PM-7:45 PM
Grand Hall CD (Manchester Grand Hyatt)
Michael Daniel Keller, MD , Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC
Catherine M. Bollard, MD , Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC
Patrick J Hanley, PhD , CETI, Blood and Marrow Transplantation, Children's National Medical Center, Washington, DC
Sarah McCormack , Children's National Medical Center, Washington, DC
Jennifer Heimall, MD , Division of Allergy and Immunology, The Children's Hospital of Philadelphia, Philadelphia, PA
Nancy Bunin, MD , Children's Hospital of Philadelphia, Philadelphia, PA
Brett Loechelt, MD , Blood and Marrow Transplantation, Children's National Medical Center, Washington, DC
Soma Jyonouchi, MD , Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA
Presentation recording not available for download or distribution as requested by the presenting author.
Background: Adoptive immunotherapy using virus-specific cytotoxic T-lymphocyte (VSTs) products has been successful in restoring antiviral immunity after hematopoietic stem cell transplantation (HSCT), and has been used to treat patients with primary immunodeficiency (PIDD).  They may also be an invaluable salvage therapy for refractory viral infections prior to HSCT.  VST can be produced from virus-exposed donors in as little as 10-14 days, and new protocols allow VST production from virus-naïve donors in 4-5 weeks. 

Objective: To evaluate the clinical efficacy of VSTs for the prevention and treatment of CMV, EBV, and Adenovirus in patients with PIDD both before and after HSCT. 

Design/Methods: VSTs were cultured from HSCT donors using peptide pulsed antigen presenting cells and cytokines.  VSTs were tested for specificity and non-alloreactivity via IFN-g ELISpot and cytotoxicity assays.  Patients were followed for 45 days following infusion for toxicity monitoring and for >6 months for antiviral response. 

Results: Five patients with PIDD who underwent HSCT were recruited to date, and two have been infused with VSTs at 5x10E6 cells/m2/dose.  The manufactured VSTs had a CD4+ T-cell predominance with detectable antiviral activity against CMV pp65/IE1, EBV-LMP2/EBNA1, and Adv-Hexon/Penton epitopes based on IFN-g ELISpot assays.  All VSTs were non-alloreactive in chromium release assays utilizing allogeneic PHA blasts as targets (<5% lysis at effector:target ratios of 20:1).  The first patient was treated for CMV viremia which was refractory to ganciclovir and foscarnet following haploidentical HSCT for SCID. Following two VST infusions, the CMV load reduced from >1,000,000 to <1000 copies/ml.  The second patient was treated for CMV viremia after matched sibling HSCT for MHC-II deficiency, and had viral clearance of CMV within 1-month post-VST infusion. One patient developed Grade I skin GVHD post VSTs which resolved within 1 week and was associated with the tapering of immune suppression.

Conclusions: VSTs are safe and effective for control of viral infections in patients with PIDD following HSCT.  We plan further evaluation of virus-specific CTL for patients with PIDD both before and after HSCT.

Disclosures:
Nothing To Disclose
See more of: Poster Session 1: Pediatric Disorders
See more of: Poster Abstracts
<< Previous Presentation | Next Presentation >>