Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 216, Issue 2, Pages 153-161Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jix203
Keywords
Parainfluenza virus 3; virus-specific T cells; immunotherapy
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Funding
- Dan L. Duncan Comprehensive Cancer Center [P30 CA125123]
- National Institutes of Health [T32 DK060445-11, T32 HL92332-12]
- American Cancer Society [MRSG-14-197-01-LIB]
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Parainfluenza virus type 3 (PIV3) infections are a major cause of morbidity and mortality in immunocompromised individuals, with no approved therapies. Our group has demonstrated the safety and efficacy of adoptively transferred virus-specific T cells for the prevention and treatment of a broad range of viral infections including BK virus, cytomegalovirus, adenovirus, human herpesvirus 6, and Epstein-Barr virus. However, this approach is restricted to well-characterized viruses with known immunogenic/protective T-cell target antigens, precluding extension to PIV3. We now characterize the cellular immune response to all 7 PIV3-encoded antigens in 17 healthy donors and define a hierarchy of immunogenicity based on the frequency of responding donors and the magnitude of specific cells. We show that reactive populations of both CD4(+) and CD8(+) T cells are capable of producing Th1-polarized effector cytokines and killing PIV3-expressing targets. Furthermore, we confirm the clinical relevance of these cells by demonstrating a direct correlation between the presence of PIV3-specific T cells and viral control in allogeneic hematopoietic stem cell transplant recipients. Taken together, our findings support the clinical use of PIV3-specific T cells produced with our Good Manufacturing Practice-compliant manufacturing process, in immunocompromised patients with uncontrolled infections.
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