Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals.
Immunocompromised individuals are at high risk for life-threatening diseases, especially those caused by cytomegalovirus (CMV), Epstein-Barr virus (EBV) and adenovirus. Conventional therapeutics are primarily active only against CMV, and resistance is frequent. Adoptive transfer of polyclonal cytotoxic T lymphocytes (CTLs) specific for CMV or EBV seems promising, but it is unclear whether this strategy can be extended to adenovirus, which comprises many serotypes. In addition, the preparation of a specific CTL line for each virus in every eligible individual would be impractical. Here we describe genetic modification of antigen-presenting cell lines to facilitate the production of CD4(+) and CD8(+) T lymphocytes specific for CMV, EBV and several serotypes of adenovirus from a single cell culture. When administered to immunocompromised individuals, the single T lymphocyte line expands into multiple discrete virus-specific populations that supply clinically measurable antiviral activity. Monoculture-derived multispecific CTL infusion could provide a safe and efficient means to restore virus-specific immunity in the immunocompromised host.
Leen
Ann M
AM
Center for Cell and Gene Therapy, Baylor College of Medicine, The Methodist Hospital and Texas Children's Hospital, Houston, Texas 77030, USA.
Myers
G Doug
GD
Sili
Uluhan
U
Huls
M Helen
MH
Weiss
Heidi
H
Leung
Kathryn S
KS
Carrum
George
G
Krance
Robert A
RA
Chang
Chung-Che
CC
Molldrem
Jeffrey J
JJ
Gee
Adrian P
AP
Brenner
Malcolm K
MK
Heslop
Helen E
HE
Rooney
Cliona M
CM
Bollard
Catherine M
CM
D000256:Adenoviridae / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000821:virology; D018929:Cell Culture Techniques / Q000379:methods*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003587:Cytomegalovirus / Q000378:metabolism; D005260:Female; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D007154:Immune System Diseases / Q000097:blood* / Q000628:therapy*; D016130:Immunophenotyping; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000378:metabolism