Interferon-gamma expressing EBV LMP2A-specific T cells for cellular immunotherapy.
To generate therapeutic T cells for adoptive immunotherapy, T cells specific to Epstein-Barr virus LMP2A were enriched on the basis of antigen-specific production of interferon-gamma (IFNgamma). The enriched T cells, contained over 60% LMP2A-specific effectors, were polyclonal and targeted multiple LMP2A epitopes. A high proportion of the enriched T cells produced the Th1 cytokines interleukin (IL)-2 and granulocyte monocyte colony stimulating factor, while few cells expressed the Th2 cytokines IL4 and IL10. The enriched T cells specifically lysed LMP2A-expressing target cells, with concomitant production of IFNgamma and surface expression of CD107, suggesting the involvement of the granule exocytosis-mediated cytolytic pathway. In addition, the enriched T cells expressed CD45RO, CD28 and CD27, but not CD45RA, consistent with a differentiation stage capable of self-renewal for long-term persistence. LMP2A-specific T cells enriched based on IFNgamma-production may provide improved efficacy for the treatment of Epstein-Barr virus related malignancy.
Division of Hematology/Oncology, Department of Pediatrics, Pennsylvania State College of Medicine, Pennsylvania State Milton S. Hershey Medical Center, Pennsylvania State Children's Hospital, 500 University Drive, Hershey, PA 17033-0850, USA. qsun@psu.edu
Qi
Q
Sun
Nargisa
N
Brewer
Kimberly
K
Dunham
Lipai
L
Chen
Lei
L
Bao
Robert
R
Burton
Kenneth G
KG
Lucas
D018106:CD28 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D000939:Epitopes / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000628:therapy*; D005089:Exocytosis; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D014412:Tumor Virus Infections / Q000628:therapy*; D014763:Viral Matrix Proteins / Q000276:immunology*
D018106:CD28 Antigens; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D000939:Epitopes; D007378:Interleukins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014763:Viral Matrix Proteins; D007371:Interferon-gamma; D017493:Leukocyte Common Antigens