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Generation and characterization of ex vivo propagated autologous CD8+ cells
used for adoptive immunotherapy of patients infected with human
immunodeficiency virus
TL Whiteside, EM Elder, D Moody, J Armstrong, M Ho, C Rinaldo, X Huang, D Torpey, P Gupta and D McMahon
Department of Pathology, University of Pittsburgh School of Medicine, PA.
Cytolytic T lymphocytes play an important role in host defense against
viral infections, including human immunodeficiency virus (HIV). In a phase
I clinical trial (protocol 080 of the AIDS Clinical Trials Group),
generation of CD8+ effector cells from peripheral blood of patients with
acquired immunodeficiency syndrome (AIDS)-related complex (ARC) or AIDS and
safety of autologous adoptive transfer of these cells were evaluated. For
therapeutic infusions, CD8+ T cells were purified by positive selection on
anti-CD8 monoclonal antibody-coated flasks from leukapheresed peripheral
blood of seven patients. These CD8+ T cells were cultured in the presence
of interleukin-2 and phytohemagglutinin for up to 3 weeks to obtain cells
sufficient for therapeutic infusions (10(8) to 10(10)). All 31 cell
cultures established from the seven patients and used for therapy were
highly enriched in CD8+ (mean, 97%), CD8+HLA-DR+ (50%), cytotoxic
CD8+CD11b- (82%), and memory CD29+ (78%) T lymphocytes. In vitro expanded
CD8+ cells had excellent cytotoxic function at the time they were used for
therapy, including HIV-specific activity against autologous targets
infected with vaccinia vectors expressing HIV-IIIb antigens, gag, pol, and
env. Anti-HIV activity of cultured CD8+ cells was significantly higher than
that of autologous fresh peripheral blood lymphocytes. Our results show
that CD8+ T lymphocytes obtained from peripheral blood of symptomatic
HIV-infected patients can be purified, cultured to obtain large numbers of
cells with enhanced anti-HIV activity, and safely infused into patients
with AIDS as a form of immunotherapy.
Volume 81,
Issue 8,
pp. 2085-2092,
04/15/1993
Copyright © 1993 by The American Society of Hematology
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