Format

Send to

Choose Destination
Cytotherapy. 2016 Dec;18(12):1515-1524. doi: 10.1016/j.jcyt.2016.08.010. Epub 2016 Sep 28.

Human parainfluenza virus-3 can be targeted by rapidly ex vivo expanded T lymphocytes.

Author information

1
Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC, USA; Division of Blood and Marrow Transplantation, Children's National Medical Center, Washington, DC, USA.
2
Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC, USA.
3
Sheikh Zayed Institute, Children's National Medical Center, Washington, DC, USA.
4
Center for Genetic Medicine Research, Children's National Medical Center, Washington, DC, USA.
5
Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC, USA; Division of Blood and Marrow Transplantation, Children's National Medical Center, Washington, DC, USA; Division of Allergy and Immunology, Children's National Medical Center, Washington, DC, USA.
6
Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC, USA; Division of Allergy and Immunology, Children's National Medical Center, Washington, DC, USA. Electronic address: mkeller@cnmc.org.

Abstract

BACKGROUND AIMS:

Human parainfluenza virus-3 (HPIV) is a common cause of respiratory infection in immunocompromised patients and currently has no effective therapies. Virus-specific T-cell therapy has been successful for the treatment or prevention of viral infections in immunocompromised patients but requires determination of T-cell antigens on targeted viruses.

METHODS:

HPIV3-specific T cells were expanded from peripheral blood of healthy donors using a rapid generation protocol targeting four HPIV3 proteins. Immunophenotyping was performed by flow cytometry. Viral specificity was determined by interferon (IFN)-γ ELISpot, intracellular cytokine staining and cytokine measurements from culture supernatants by Luminex assay. Cytotoxic activity was tested by 51Cr release and CD107a mobilization assays. Virus-specific T cells targeting six viruses were then produced by rapid protocol, and the phenotype of HPIV3-specific T cells was determined by immunomagnetic sorting for IFN-γ-producing cells.

RESULTS:

HPIV3-specific T cells were expanded from 13 healthy donors. HPIV3-specific T cells showed a CD4+ predominance (mean CD4:CD8 ratio 2.89) and demonstrated specificity for multiple HPIV3 antigens. The expanded T cells were polyfunctional based on cytokine production but only had a minor cytotoxic component. T cells targeting six viruses in a single product similarly showed HPIV3 specificity, with a predominant effector memory phenotype (CD3+/CD45RA-/CCR7-) in responder cells.

DISCUSSION:

HPIV3-specific T cells can be produced using a rapid ex vivo protocol from healthy donors and are predominantly CD4+ T cells with Th1 activity. HPIV3 epitopes can also be successfully targeted alongside multiple other viral epitopes in production of six-virus T cells, without loss of HPIV3 specificity. These products may be clinically beneficial to combat HPIV3 infections by adoptive T-cell therapy in immune-compromised patients.

KEYWORDS:

antiviral therapy; cytotoxic T-lymphocytes; human parainfluenza; immunodeficiency; immunotherapy

PMID:
27692559
PMCID:
PMC5096976
DOI:
10.1016/j.jcyt.2016.08.010
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center