Retroviral transduction of a T cell receptor specific for an Epstein-Barr virus-encoded peptide.
The Type II EBV malignancies nasopharyngeal carcinoma and EBV(+) Hodgkin's disease express three subdominant antigens, latency membrane protein (LMP) 1, LMP2, and EBNA-1. While adoptive immunotherapy with T cell lines for Type III EBV malignancy (such as posttransplant lymphoma, PTLD, which expresses the immunodominant EBNA-3 antigens) has been used to prevent and treat PTLD, the generation of class I MHC-restricted CTL suitable for the immunotherapy of Type II EBV malignancy is difficult. This is primarily due to the lack of anti-LMP or EBNA-1 CTL activity in many healthy volunteers. We have engineered, by retroviral transduction of the TCR, CTL that have the potential to recognize subdominant EBV latency antigens. Using the SAMEN retroviral vector we demonstrate the ability to transfer CTL activity from a LMP2 peptide-specific CTL clone to a stimulated PBMC population. TCR-transduced PBMC also secrete IFN-gamma upon coculture with LMP2 targets and maintain expression of the transduced TCR during subsequent mitogenic expansion.
Orentas
R J
RJ
Section of Hematology-Oncology, Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin, 53226, USA.
Roskopf
S J
SJ
Nolan
G P
GP
Nishimura
M I
MI
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005822:Genetic Vectors / Q000235:genetics*; D015789:HLA-A2 Antigen / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D009052:Leukemia Virus, Murine / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D000939:Epitopes; D015789:HLA-A2 Antigen; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014763:Viral Matrix Proteins; D007371:Interferon-gamma