Generation and characterization of ex vivo propagated autologous CD8+ cells used for adoptive immunotherapy of patients infected with human immunodeficiency virus.
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.
Whiteside
T L
TL
Department of Pathology, University of Pittsburgh School of Medicine, PA.
Elder
E M
EM
Moody
D
D
Armstrong
J
J
Ho
M
M
Rinaldo
C
C
Huang
X
X
Torpey
D
D
Gupta
P
P
McMahon
D
D
D000386:AIDS-Related Complex / Q000628:therapy*; D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy*; D000328:Adult; D000911:Antibodies, Monoclonal; D016827:CD8 Antigens / Q000276:immunology; D002469:Cell Separation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000494:pharmacology; D007937:Leukapheresis; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000637:transplantation*
D000911:Antibodies, Monoclonal; D016827:CD8 Antigens; D007376:Interleukin-2; D010835:Phytohemagglutinins