Page 29 - 2019秋季手冊內頁-ebook測試

演講摘要
ABSTRACT
EBV and Cancers: Focusing on “Development Of T-Cell Therapies for EBV” presented by Cliona Rooney in the SITC 2019 meeting
陳榮隆/和信治癌中心醫院小兒血液腫瘤科
Introduction of Epstein-Barr Virus (EBV) and Cancers
• Herpesvirus present in clams since over 300 million years and other species
• EBV belongs to -herpesvirus
• Inhumans:EBVpersistsforlifeinBlymphocytes(expressupto9latentcycleproteins)
and oropharyngeal epithelial cells ( express about 80 lytic cycle proteins)
• EBV primary infections: asymptomatic to infectious mononucleosis (IM) or
hemophagocytic lymphohistiocytosis (HLH)
• EBV lymphoproliferative diseases (LPD): Post-transplant lymphoproliferative disease
(PTLD) and other immunodeficiency-associated, Hodgkin lymphoma, EBV-associated
diseases of NK cells and T cells
• EBV and epithelial cancers: nasopharyngeal carcinoma, gastric carcinoma
• TransmissionofEBVinHumans(DavidThorley-Lawson)throughsaliva(10e2-10e8/ml
EBV particles) with excretion of 2x10e4-7.2x10e10 per day
• EBV Latency Programs: Latency I: EBNA1, BARF1 (Burkitt’s lymphoma); Latency II: I+
LMP1, LMP2 (Hodgkin’s lymphoma, NHL, Nasopharyngeal carcinoma, Gastric adenocarcinoma); Latency III: II+ EBNAs 2,3a,3b,3c, LP (Immunodeficiency associated lymphoma)
• PTLD(byHelenHeslopandMalcolmBrenner,ExperienceinSJCRH1990-1998): Incidence of PTLD in HSCT recipients was ~15%; Associated with T cell depletion; Donor leukocyte infusions benefitted some patients but with severe GVHD; Could selectively expanded EBV-specific T cells (EBVST) provide benefit w/o GVHD? Yes
Developments of EBVST
(1) LCL-activated EBV-specific T-cells (LCL-EBVST) Manufacturing (Wallace, Rickinson and Moss)
• B95-8 strain to generate EBV-LCL
• EBVSTs from PBMCs about 3-6 weeks
• EBVST specificity including EBNA 3a, b, c, LMP 2, EBNA2, EBNA-LP, LMP 1, EBNA1
and ZEBRA, BMLF-1, BRLF1, Other lytic antigens
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